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CEREBROSPINAL  FLUID  IN 
HEALTH  AND  IN   DISEASE 


CEREBROSPINAL  FLUID 

IN  HEALTH  AND  IN  DISEASE* 


ABRAHAM  LEVINSON,  B.S.,  M.D. 

ASSOCIATE   IN   PEDIATRICS,    NORTHWESTERN   UNIVERSITY   MEDICAL    SCHOOL;    ASSO- 
CIATE    PEDIATRICIAN,     SARAH     MORRIS     CHILDREN  'S     HOSPITAL     OF     THE 
MICHAEL     REESE     HOSPITAL,     CHICAGO;      ATTENDING     PEDIATRI- 
CIAN,   MOUNT    SINAI    HOSPITAL,    CHICAGO;    ATTENDING 
-     PHYSICIAN,    children's    DEPARTMENT,    CHI- 
CAGO-WINFIELD    TUBERCULOSIS 
SANITARIUM 


WITH  A  rOREWOED  BY 

LUDVIG  HEKTOEN,  M.D. 


WITH  FIFTY-SIX  ILLUSTRATIONS,  INCLUDING 
FIVE  COLOR  PLATES 


ST.  LOUIS 

C.  V.  MOSBY  COMPANY 

1919 


Copyright,  1919,  By  C.  V.  Mosby  Cojipany 


Press  of 

C.    V.   Mosby    Coml^any 

St.  Louis 


To  Him  to  Whom  the  Practice  of  Medi- 
cine Constitutes  an  Ideal  Rathek 
Than  a  Profession, 

To  Him  Who  Combines  Clinical  Insight 
AND  Scientific  Research, 

To  Him  Who  Sees  in  Medicine  Both  a 
Science  and  a  Philosophy, 

This  Little  Volume  is  Respectfully 
Dedicated. 


FOREAVORD 
By  Ludvig  Hektoen,  M.D. 

The  author  was  kind  enough  to  ask  me  if  I  would  look 
over  his  manuscript  and  then  tell  him  whether  it  seemed  to 
me  worthy  of  publication.  Later,  when  I  told  him  that  in 
my  opinion  he  had  produced  a  valuable  little  book,  he  re- 
quested me  to  state  the  reasons  for  this  favorable  opinion 
in  the  form  of  a  foreword.  This  I  can  do  in  a  few  brief 
statements. 

In  the  first  place,  on  reading  the  manuscript,  I  soon  be- 
came aware  that  the  author  had  come  to  his  task  with  not 
only  a  large  experience  behind  him  in  the  examination  by 
various  methods  of  the  cerebrospinal  fluid  as  an  aid  in 
diagnosis,  but  with  a  highly  creditable  record  in  the  sci- 
entific study  of  this  fluid  as  well.  Evidently  he  had  been 
drawn  to  his  work  on  the  cerebrospinal  fluid  because  of 
its  attractiveness  as  a  field  of  research,  as  well  as  on  ac- 
count of  its  importance  in  diagnosis. 

It  is  to  this  happy  combination  of  true  philosophic  inter- 
est and  first-hand  practical  knowledge  on  the  part  of  the  au- 
thor that  the  book  owes  its  chief  merit,  namely,  thorough- 
ness and  freshness  in  the  parts  dealing  with  fundamental 
problems,  as  well  as  in  those  dealing  with  practical  mat- 
ters. In  the  second  place  there  could  be  no  doubt  in  re- 
gard to  the  timeliness  of  a  w^ork  of  this  kind.  Indeed  it 
seemed  to  me  that  a  definite  want  would  be  supplied;  for, 
in  spite  of  an  increasing  importance  in  medicine,  there 
was  as  yet  no  comprehensive  book  on  all  phases  of  the 
cerebrospinal  fluid. 

Jolin  McCormic'k  Institute 

For  Infectious  Diseases,  Chicago. 

7 


PREFACE 


Of  recent  years  the  study  of  body  fluids  lias  been  engag- 
ing the  attention  of  many  phj^sicians  and  scientists.  Par- 
ticularly marked  has  been  the  interest  in  the  study  of  cere- 
brospinal fluid.  Through  recent  investigations  of  this  fluid, 
we  have  gained  a  great  deal  of  information  regarding  the 
diagnosis  and  nature  of  many  diseases  and  a  much  clearer 
conception  of  the  general  physiologic  processes  in  the  body. 
Further  investigations  on  the  subject  will  open  up  new 
possibilities  in  science  and  medicine,  for  there  is  hardly  an- 
other body  fluid  that  presents  so  favorable  an  opportunity 
for  the  study  of  physiologic  and  pathologic  processes  in 
the  human  body  as  the  cerebrospinal  fluid. 

Cerebrospinal  fluid  is  of  great  physiologic  importance 
for  various  reasons.  It  is  the  clearest  and  most  transpar- 
ent of  all  the  fluids  of  the  body.  It  is  clearer  than  blood, 
than  bile,  and  even  clearer  than  urine,  and  under  normal 
conditions  experiments  may  be  made  on  it  without  fear 
of  clot  formation  or  color  change.  Furthermore,  cerebro- 
spinal fluid,  like  blood  and  urine,  can  be  removed  from  the 
living  body  wdthout  injury  to  the  system.  This  gives  one 
the  opportunity  of  working  with  processes  in  the  living 
body — a  distinct  advantage  oA^er  the  study  of  dead  tissue. 

From  the  standpoint  of  pathology  also,  cerebrospinal 
fluid  presents  an  exceptional  opportunity  for  study.  The 
slightest  change  in  the  color  of  the  fluid,  the  smallest  in- 
crease in  the  protein  content  or  in  the  cell  count,  all  of 
which  are  easily  discernible,  indicate  the  presence  of  a 
pathologic  process.  One  is  able  to  follow  the  course  of 
disease  throughout  all  stages  by  noting  the  various  changes 

9 


10  PREFACE 

the  cerebrospinal  fluid  undergoes  from  time  to  time.  These 
changes  may  be  manifested  not  only  by  the  presence  of 
the  causative  organisms  themselves,  but  just  as  frequently 
by  specific  physical,  chemical,  cytologic  and  physicochem- 
ical  processes.  A  close  study  of  the  changes  in  the  cere- 
brospinal fluid  under  pathologic  conditions  throws  light, 
not  only  on  the  specific  diseases  of  the  nervous  system,  but 
on  the  condition  of  other  systems.  One  can  readily  see, 
therefore,  how  large  is  the  scope  for  the  study  of  cerebro- 
spinal fluid. 

In  this  book  I  shall  discuss  cerebrospinal  fluid  in  its  vari- 
ous phases,  aiid  shall  attempt  to  show  the  nature  of  the 
fluid  in  its  normal  state  and  to  point  out  the  deviations  in 
processes  of  disease.  I  shall  incorporate  the  results  of 
my  owTi  clinical  and  experimental  studies  as  well  as  the 
observations  of  the  many  workers  who  have  added  to  our 
knowledge  by  their  researches  on  cerebrospinal  fluid. 

This  little  book  is  sent  out  as  an  hmnble  contribution,  as 
I  am  fully  aware  of  its  many  shortcomings  and  omissions ; 
but  if  it  saves  the  busy  practitioner  the  irksome  task  of 
consulting  countless  sources  for  information  on  cerebro- 
spinal fluid,  I  shall  feel  that  the  work  has  not  been  in  vain. 
And  if  perchance  it  should  serve  to  stimulate  even  one 
zealous  student  to  help  solve  some  of  the  problems  pre- 
sented, I  shall  feel  that  my  effort  has  been  amply  rewarded. 

Many  of  the  investigations  that  have  found  their  way 
into  this  volume  would  not  have  been  possible  without  the 
constant  cooperation  of  certain  institutions  and  individ- 
uals. I,  therefore,  take  this  opportunity  of  expressing  my 
gratitude  to  them  collectively  and  individually — to  the  at- 
tending staff,  internes  and  nurses  of  the  Michael  Reese 
Hospital  in  general,  and  the  Sarah  Morris  Hospital  for 
Children  in  particular,  to  Dr.  Katharine  Howell,  serol- 
ogist  of  the  Xelson  ]\Iorris  Institute  for  Medical  Re- 
search, to  Professor  F.  C.  Becht  of  the  Department  of 
Pharmacology  of  the  Xorthwestern  University,  and  to  Dr, 


PEEFACE  11 

G.  Bartehnez  of  tlie  Department  of  Anatomy,  University 
of  Chicago. 

Particular  thanks  are  due  to  Professor  Ludvig  Hektoen 
of  the  University  of  Chicago  for  his  helpful  suggestions 
and  for  his  careful  reading  of  the  manuscript,  and  to  Pro- 
fessor Shiro  Tashiro  of  tlie  Department  of  Biochemistry  of 
the  University  of  Cincinnati  for  his  tireless  assistance  in 
checking  up  many  of  the  experiments.  Thanks  are  also 
due  the  editors  and  publishers  of  the  many  journals  for 
their  permission  to  republish  some  of  my  articles  that  ap- 
peared in  their  journals. 

A.  Levinson. 

Chicago,  111. 


CONTENTS 

OHAPTEE  I 

PAGK 

History  of  Cerebkospinal  Fluid       17 

CHAPTER  II 

Anatomy  and  Physiology  of  Cerebrospinal  Fluid 30 

Location,  30;  Formation  and  Absorption,  34;  Permeability,  38; 
Function,  40;  Origin,  41. 

CHAPTER  III 

Methods  of  Obtaining  Cerebrospinal  Fluid  from  the  Living  Body     .      49 
Lumbar   Puncture,   49;    Untoward   Effects   of   Lumbar   Puncture, 
53;    Technic    of    Lumbar    Puncture,    54;    The    Spinal    Puncture 
Needle,  57;   Reasons  for  Failure  to  Obtain  Fluid,  (i3;   Pressure, 
64;  Collection  of  the  Fluid,  69;  Cranial  Puncture,  71. 

CHAPTER  IV 

Properties  of  Normal  Cerebrospinal  Fluid 75 

Physical  Properties,  76;  Amount,  76;  Color,  76;  Lack  of  Sedi- 
ment, 76;  Pressure,  77;  Specific  Gravity,  79;  Chemical  Composi- 
tion, 79;  Physicochemical  Properties,  94;  Specific  Gravity,  94; 
Viscosity,  95;  Conductivity,  95;  Surface  Tension,  95;  Freezing 
Point,  95;  Refractometric  Index,  96;  Reaction  of  Normal  Cere- 
brospinal Fluid,  96;  Alkaline  Reserve,  105;  Biochemical  Proper- 
ties, 107;  Amylolytic  Power,  107;  Proteolytic  Power,  107;  Gly- 
colytic Ferment,  107;  Fibrin  Ferment,  107;  Alexin,  107;  Hemoly- 
sin, 108;  Toxicity,  108;  Bactericidal  Action,  108;  Cytology,  108; 
Type  of  Cell,  110. 

CHAPTER  V 

Pathologic  Cerebrospinal  Fluid 113 

Increase  in  Amount  of  Fluid,  116;  Pressure,  116;  Foam,  117; 
Cells,  117;  Pellicle,  118;  Crystallization,  120;  Permanganate  or 
Organic  Index,  123;  Protein,  125;  Precipitation,  125;  Sugar,  129; 
Turbidity,  131;  Physical  Chemistry,  132;  Protein  Charges,  133; 
The  Colloidal  Gold  Reaction,  137;  Mastic  Reaction,  137;  Ninhy- 
drin  Reaction,  137 ;  Clianges  in  the  Reaction  of  the  Cerebrospinal 
Fluid,  138;  Bacteriologic,  146;  Immunologic,  147;  Agglutination, 
147;   Hemolysin,   147;   Wassermann   Reaction,   148. 

13 


14  CONTENTS 

CHAPTER  VI 

Methods  op  Examination   op  Cerebrospinal  Fluid   por  Diagnostic 

Purposes 150 

Physical,  150;  Color,  150;  Foam,  151;  Pellicle,  151;  Cliemical,  152; 
Increase  of  Protein,  152;  Globulin  Tests,  153;  Noguclii,  154;  Ross- 
Jones,  154;  Nonne-Apelt,  154;  Kaplan  Method,  155;  Pandy,  155; 
Sulphosalieylic  Mercuric  Chloride  Method,  155 ;  Relative  Value  of 
the  Globulin  Tests,  156;  The  Permanganate  Test,  157;  Sugar, 
158;  Chlorides,  161;  Physicochemical  Methods,  162;  Lange  Gold 
Chloride  Test,  164;  Mastie  Test,  166;  Cytologic  Examination, 
167;  The  French  Method  of  Cell  Counting,  167;  Chamber  Method 
of  Cell  Counting,  168;  Comparative  Value  of  the  Two  Methods, 
169;  Type  of  Cells,  170;  Bacteriologic,  171;  Culture  Media,  171; 
Direct  Smear,  172;  Immunologic,  172;  Macroscopic  Method,  172; 
Microscopic  Method,  175;  Precipitation  of  Cerebrospinal  Fluid 
with  Antimeningococcus  Serum,  176;  Guinea  Pig  Inoculation, 
177;  Neutralization  Test,  177;  The  Wassermann  Reaction,  177. 

CHAPTER   VII 

Cerebrospinal  Fluid  in  Various  Disilases 183 

Uremia,  183;  Diabetes  Mellitus,  183;  Chorea,  183;  Epilepsy,  184; 
Mongolian  Idiocy,  184;  Psychoses,  185;  Lues,  185;  Hydrocepha- 
lus, 188;  Spina  Bifida,  188;  Hemorrhage  of  the  Brain,  188;  Tu- 
mors of  the  Brain,  189;  Compression  of  the  Cord,  189;  Encepha- 
litis, 189;  Meningism,  190;  Tuberculous  Meningitis,  190;  Men- 
ingococcus Meningitis,  194;  Pneumococcus  Meningitis,  200; 
Streptococcus  Meningitis,  202;  Influenza  Meningitis,  203;  Colon 
Meningitis,  203;  Syphilitic  Meningitis,  203;  Cerebrospinal  Fluid 
in  Poliomyelitis,  205. 

CHAPTER  VIII 

Intraspinal  Treatment 209 

Intraspinal  Treatment  of  Meningococcus  Meningitis,  209;  Unto- 
ward Effects  of  Serum,  216;  Aggravation  of  Symptoms,  217;  Serum 
Rash,  217;  Intraspinal  Treatment  of  Pneumococcus  Meningitis, 
217;  Intraspinal  Treatment  in  Tuberculous  Meningitis,  219;  Influ- 
enza Meningitis,  219 ;  Poliomyelitis,  219 ;  The  Swift-Ellis  Treatment, 
220;  Intraspinal  Treatment  of  Tetanus,  221;  Intraspinal  Treatment 
of  Chorea,  222. 

CHAPTER  IX 

Summary 224 

APPENDIX 
Appendix         226 


ILLUSTRATIONS 

FIG.  PAGE 

1.  Albertus   cle   Haller 20 

2.  Francois  Mageiidie 22 

3.  Lumbar  region  of  skeleton  of  a  one-year-old  child 26 

4.  Lumbar  region  of  skeleton  of  a  six-year-old  child 27 

5.  Section   of   human  brain    (Color   Plate) 30 

6.  Diagram    of    Tig.    5 32 

7.  Chorioid   plexus    detached    from    the    ventricles 33 

8.  Specimen   illustrating  the   importance   of   spinal   puncture   for   diag- 

nostic purposes 50 

9.  Opposite    view    of    Fig.    8 ^ 51 

10.  Section  of  cauda  equina  of  a  dog 55 

11.  Plexus    of    veins,    the    puncture    of    which    is    responsible    for    blood 

obtained  during  spinal   puncture 50 

12.  Various  types  of  lumbar  puncture  needles 58 

13.  Modified  Quincke  apparatus  for  measuring  the  cerebrospinal  fluid 

pressure 65 

14.  Author's   spinal   puncture   needle   and    manometer 67 

15.  Photograph  showing  ventricular  puncture  in  an  infant  (front  view)  72 

16.  Photograph   showing   ventricular   puncture   in   infant    (side   view)  73 

17.  Crystallization    of   nonmeningitie    cerebrospinal  iluid 89 

18.  Crystals  of  evaporated   nonmeningitie  cerebrospinal  fluid     ....  90 

19.  Crystals  of  sodium  chloride  in  a  1  per  cent  solution  of  dextrose  90 

20.  Average  change  in  the  H-ion  concentration  of  nonmeningitie  fluid 

on   standing 99 

21.  Change  in  H-ion  concentration  of  nonmeningitie  fluids   on  stand- 

ing at  room  temperature  under  various  conditions 103 

22.  Photomicrograph  of  stained  pellicle  from  cerebrospinal  fluid  of  a 

pneumococcus  meningitis 119 

23.  Pellicle  formation  in  miningitis 120 

24.  Crystals  formed  in  test  tube  on  spontaneous  evaporation  of  cere- 

brospinal fluid  from  a  case  of  tuberculous  meningitis     ....  121 

25.  Spontaneously  evaporated  cerebrospinal  fluid  from  a  case  of  tubercu- 

lous   meningitis          121 

26.  Spontaneously  evaporated  cerebrospinal   fluid   from  a  case  of  pneu- 

mococcus   meningitis 121 

27.  Crystals   froiii  an  evaporated   fluid   in  a  case  of  tuberculous  menin- 

gitis       122 

28.  Crystals  from  an  evaporated  fluid  of  a  case  of  pneumococcus  men- 

ingitis       123 

29.  Photograph  showing  the  typical  ratio  of  precipitates  by  the  two 

precipitants 126 

15 


16  ILLUSTRATIOXS 

30.  Apparatus  for  eataphoresis  of  proteins 134 

31.  Change  in  the  H-ion  concentration  of  three  types  of  cerebrospinal 

fluid 142 

32.  Different   effects   of  corking   on  tuberculous  and   epidemic   fluids     .  144 

33.  Fuchs-Eosenthal    chamber   for   counting   cells   in   cerebrospinal   fluid  168 
.34.  Neubauer  blood  counting  chamber  which  may  be  used  for  cerebro- 
spinal   fluid IfiS 

3.5.  Photograph   showing   agglutination   of   meningococci   by   the   macro- 
scopic method 173 

36.  Microscopic   method   of   agglutinating   meningococci 174 

37.  Agglutination  of  meningococci  by  the  microscopic  method     .     .     .  175 

38.  Lange  colloidal  gold  test  in  case  of  cerebrospinal  lues     ....  187 

39.  Lange   colloidal   gold   test   in   case   of   tabes 187 

40.  Lange  colloidal  gold  test  in  case  of  general  paresis 187 

41.  Lange    gold    chloride    reaction   in    a    case    of   tabes    dorsalis    (Color 

Plate) 188 

42.  Lange  gold  chloride  reaction  in  a  case  of  general  paresis   (Color 

Plate) 188 

43.  Lange  colloidal  gold  test  in  a  case  of  tuberculous  meningitis     .     .     192 

44.  Lange  gold  chloride  reaction  in  a  case  of  tuberculous  meningitis 

(Color  Plate) 192 

4.5.  Lange  gold  chloride  reaction  in  a  case  of  meningococcus  meningitis 

(Color  Plate) 19o 

46.  Lange  colloidal  gold  test  in  a  case  of  meningococcus  meningitis     .     195 

47.  Photomicrograph   showing   direct   smear    from    cerebrospinal    fluid 

'         of   case    of    meningococcus    meningitis 196 

48.  Twenty-four-hour   culture   of   meningococci   grown   in   ascitic    dex- 

trose agar 197 

49.  Photomicrograph    of    pure    meningococcus    culture 198 

50.  Photomicrograph  of  smear  from  cerebrospinal  fluid  of  pneumococ- 

cus   meningitis 201 

51.  Photomicrograph  showing  direct  smear  from  cerebrospinal  fluid  of 

case   of  mixed   strei)tococcus   and   pneumococcus   meningitis     .     201 

52.  Photomicrograph  showing  direct  smear  from  cerebrospinal  fluid  of 

case  of  influenza  meningitis 204 

53.  Photomicrograph  of  pure  culture  of  influenza  bacilli 204 

54.  Lange   colloidal   gold   test  in   case  of  epidemic   poliomyelitis     .     .  205 

55.  Instrument  for  the  introduction  of  antimeningococ«us  serum  by  the 

gravity   method 212 

56.  Temperature  and  pulse  chart  of  a  case  treated  by  antimeningococcus 

serum 214 


CEREBROSPINAL  FLUID 


CHAPTER  I 

HISTORY  OF  CEREBROSPINAL  FLUID 

The  existence  of  water  on  the  brain  in  pathologic  cases 
Avas  knoA\Ti  to  the  ancients.  Hippocrates  is  credited  with 
tapping  the  ventricles  in  hydrocephalus.  We  have  nothing 
to  show,  however,  that  the  ancients  knew  of  the  existence 
of  fluid  in  normal  persons.  There  is  no  mention  of  cere- 
brospinal fluid  in  the  early  writings  of  Hippocrates.  In 
the  later  Hippocratedian  collection  the  brain  is  spoken  of 
as  a  gland.  The  glandular  nature  of  the  brain  in  this  in- 
stance, however,  does  not  refer  to  the  cerebrospinal  fluid, 
but  to  the  so-called  secretion  which  the  ancients  believed 
was  poured  down  from  the  brain  into  the  pharynx.  Heroph- 
ilus  in  his  writings  shows  that  he  knew  of  the  existence 
of  the  ventricles  and  of  the  chorioid  plexus,  but  not  of  the 
function  of  the  chorioid  plexus  or  of  the  contents  of  the 
ventricles.  It  seems  but  natural  to  suppose  that  Heroph- 
ilus  who  dissected  hundreds  of  human  bodies  should 
have  known  of  the  existence  of  cerebrospinal  fluid  in  the 
ventricles.  We  wonder  if  it  could  be  possible  for  so  keen 
an  observer  as  he  not  to  notice  the  presence  of  a  large 
amount  of  fluid  in  the  cavity  of  the  brain  on  cutting  it  open. 
Yet,  in  giving  a  description  of  the  ventricles  which  he 
speaks  of  as  the  seat  of  the  soul,  he  makes  not  the  slightest 
reference  to  the  presence  of  any  fluid  in  the  brain.  There 
is  a  possibility,  of  course,  that  the  lost  books  of  Herophilus 
may  have  contained  some  reference  to  cerebrospinal  fluid. 

One  finds  the  same  silence  on  the  subject  in  other  ancient 

17 


18  CEREBROSPINAL  FLUID 

authorities.  Erasistratus  of  Julis  (330-250)  describes 
four  cavities  in  the  brain,  but  he  makes  no  mention  of  fluid 
in  them.  Galen,  Avho  Avas  thoroughly  familiar  with  the 
construction  of  tlie  ventricles,  speaks  of  an  "excrementi- 
tial  liquid,  expressed  from  several  places  in  the  brain  into 
the  ventricles,  especially  the  fourth,  where  this  liquid  is 
stored  and  then  purged  into  the  nose  through  the  ethmoid 
bones  and  inf undibulum. ' '  The  fluid  referred  to,  however, 
may  not  be  the  cerebrospinal  fluid.  Hemesius  of  Emersa 
(born  340  a.d.)  gives  a  minute  analysis  of  the  ventricles 
and  the  localization  of  mental  power  within  them,  but  he 
does  not  speak  of  the  fluid  they  contain.  One  would  nat- 
urally turn  to  Vesalius  for  a  description  of  cerebrospinal 
fluid,  for  it  is  a  well-known  fact  that  Vesalius  knew  the 
ehorioid  plexus  and,  tlierefore,  must  also  have  observed  the 
fluid.  Yet,  though  he  devotes  page  upon  page  to  a  discus- 
sion of  the  localization  of  the  soul,  he  merely  mentions  a 
watery  humor  of  the  brain,  but  gives  no  descrij)tion  of  anj^ 
humor  that  would  indicate  that  he  had  the  cerebrospinal 
fluid  in  mind.  Mention  of  the  presence  of  a  fluid  in  the 
brain  is  found  in  the  writings  of  Varolius  (1543-1575). 
This  scientist,  who  described  the  pons  that  bears  his  name, 
denied  the  existence  of  pneuma  in  the  ventricles,  and  in- 
sisted that  it  was  fluid  and  not  pneuma  that  filled  up  the 
cavity  of  the  ventricles.  However,  he  gives  no  description 
of  the  fluid  he  recognized.  The  real  discovery  of  cerebro- 
spinal fluid  is  attributed  to  Contugno.  Dominico  Contugno 
is  responsible  for  many  discoveries  in  medicine.  He  dis- 
covered intestinal  lesions  postmortem  in  a  ease  of  tj^phoid; 
demonstrated  the  presence  of  albumin  in  urine  on  boiling; 
and  discovered  the  aqueduct  in  the  internal  ear  known 
su])sequently  as  the  aqueductus  Contugni.  In  1784  he  made 
the  important  discovery  of  the  presence  of  cerebrospinal 
fluid  in  living  fishes  and  turtles,  although  he  could  not  de- 
tect its  presence  in  man.  Though  Contugno  usually  gets 
the  credit  for  the  discovery    of    the    cerebrospinal  fluid, 


HISTOKY  19 

Bilanclioni  claims  that  Valsalva  prior  to  Contugno  found 
"an  ounce  of  a  certain  liquid  in  cutting  the  cord  membrane 
of  a  dog,  a  fluid  resembling  that  seen  in  articulations." 

The  absence  of  a  method  whereby  normal  cerebrospinal 
fluid  could  be  demonstrated  in  living  beings  was  respon- 
sible for  the  lack  of  interest  shown  in  the  investigations  of 
this  fluid.  Whatever  interest  there  was,  was  confined  to 
pathologic  cases.  In  1727  Stalpartius  Vander  Wiel  de- 
scribed a  case  of  injury  to  the  head  in  which  a  clear  watery 
fluid  was  seen  to  escape  from  the  ear  for  several  days  after 
the  injury.  In  1764  Robert  Whytt  appeared  with  a  descrip- 
tion of  tuberculous  meningitis.  He  divided  the  disease  into 
three  stages  according  to  the  behavior  of  the  pulse,  and 
attributed  the  various  manifestations  of  the  disease  to  the 
presence  of  a  serous  exudate.  In  1768  he  published  the 
results  of  his  work  on  acute  hydrocephalus  under  the  title 
*' Observations  on  Dropsy  of  the  Brain."  Under  the  head- 
ing of  acute  hydrocephalus  he  included  all  forms  of  acute 
brain  disease. 

For  a  clear-cut  description  of  cerebrospinal  fluid  in  nor- 
mal persons  we  must  turn  to  the  writings  of  Albertus  de 
Haller  (Fig.  1).  In  the  "First  Lines  of  Physiology"  in 
the  third  Latin  translation,  we  find  the  following  descrip- 
tion : 

"The  fluids,  which,  being  deposited  from  the  blood  into 
other  vessels,  are  said  to  be  secreted,  seem  reducible  to 
four  classes.  The  first  consists  of  viscid  fluids,  coagulable 
by  a  heat  of  about  150°,  by  alcohol,  and  by  strong  acids, 
although  generally,  in  the  living  animal,  they  escape  in  the 
form  of  vapor  and  after  death  are  compacted  into  a  gela- 
tinous substance.  To  this  class  belong  the  liquor  and  hali- 
tus  of  the  ventricles  of  the  brain,  the  pericardium,  pleura, 
peritoneum,  tunica  vaginalis,  amnois,  joints,  renal  capsules, 
and  probably  of  the  womb,  with  the  juices  of  the  stomach 
and  intestines,  and  lastly  the  lymph  generally  knowm." 

A  little  further  TTaller  goes  on  as  follows: 


20 


CEREBROSPINAL  FLUID 


"Have  lymphatic  vessels  been  seen  with  certainty  in  the 
brain?  They  have  been  described  in  the  large  chorioidal 
plexus  amongst  the  fibers  of  the  olfactory  nerve,  and  in  the 
pia  mater.  For  my  own  part,  I  have  never  seen  them,  and 
it  is  probable  that  there  are  none,  since  there  are  no  con- 
glomerate glands  in  the  brain,  which  are  always  found 
near  these  vessels.  As  for  the  various  accounts  which  are 
given  of  the  pituitary  glands,  to  the  infundibulum  and  of 
the  ducts  which  lead  from  thence  into  the  veins  of  the  head, 
absorbing  water  from  the  ventricles,  they  are    not    sup- 


Fig.   1.— Alhertus  de   Mailer   (1708-1777). 

ported  by  any  anatomic  demonstration;  which  makes  it 
probable  that  the  vapor,  which  is  secreted  into  the  ventri- 
cles of  a  healthy  person,  is,  in  like  proportion,  absorbed 
again  by  the  inhaling  veins ;  and  that  if  there  be  any  excess, 
it  descends  through  the  bottom  of  the  ventricles  to  the 
basis  of  the  skull,  and  into  the  loose  cavity  of  the  spinal 
marrows  That  this  is  the  case,  appears  from  the  palsies, 
which  ensue  after  apoplexies  and  from  the  watery  tumors 
in  the  lower  part  of  the  spinal  marrow,  in  hydrocephalic 
patients. ' ' 


HISTORY  21 

Ilaller  thought  that  the  fluid  not  only  was  secreted  in  the 
hollow  tubes  of  the  medulla,  but  that  it  also  flowed  into  the 
small  tubes  of  the  nerves.  In  the  quotation  that  follows 
may  be  found  part  of  Haller's  explanation  of  the  mechan- 
ism of  irritability,  the  original  conception  of  which  was 
advanced  by  Glisson. 

"Upon  the  whole,  it  seems  to  be  certain  that,  from  the 
vessels  of  the  cortex,  a  liquor  is  secreted  into  the  hollow 
tubes  of  the  medulla,  which,  being  continued  into  the  small 
tubes  of  the  nerves,  and  propelled  to  their  extremities,  is 
the  cause  of  both  sense  and  motion.  But  there  will  be  a 
twofold  motion  in  that  hmnor;  the  one  slow  and  constant 
from  the  heart;  the  other,  not  continual,  but  exceedingly 
swift,  which  is  excited  either  by  sense  or  any  cause,  as 
motions  arising  in  the  brain." 

It  is  evident  from  Haller's  own  statement  that  he  knew 
of  the  existence  of  cerebrospinal  fluid  in  the  ventricles  and 
of  the  course  of  its  circulation.  However,  with  all  his 
knowledge  he  does  not  seem  to  have  been  aware  of  the  real 
nature  and  composition  of  the  fluid.  It  was  left  to  Magen- 
die  (Fig.  2)  (1825)  to  give  us  an  accurate  description  of 
the  workings  of  the  fluid,  especially  the  fluid  at  the  base 
of  the  brain.  We  are  indebted  to  him  for  a  clear-cut  con- 
ception of  the  physical  appearance  and  protective  func- 
tion of  the  cerebrospinal  fluid.  The  following  is  taken 
from  Magendie's  treatise  on  Physiology: 

''But  there  is  a  disposition  unknown  to  Bichat,  which  I 
have  recently  discovered,  and  which  contributes  in  a  man- 
ner extremely  efficacious  to  the  conservation  and  defense 
of  the  medulla. 

''The  canal  which  is  formed  around  the  medulla  by  the 
pia  mater,  and  which  is  lined  by  the  arachnoid,  is  a  great 
deal  larger  than  is  necessary  to  contain  the  organ ;  but  dur- 
ing life  the  whole  interval  is  filled  up  by  a  serous  liquid, 
which  strongly  distends  the  membrane  and  which  spouts 
out  to  many  inches  in  height  from  a  small  puncture  made 


22 


CEREBROSPINAL  FLUID 


in  the  dura  mater.  An  analogous  arrangement  is  also  to 
be  observed  around  the  brain  and  cerebellum.  It  is  easy 
to  conceive  how  efficacious  must  be  the  protection  thus  de- 
rived from  the  liquid  which  surrounds  the  spinal  marrow, 
and  in  the  midst  of  which  it  is  suspended  like  the  fetus  in 
utero;  with  this  difference  that  it  is  fixed  in  its  position 
by  the  ligamentum  dentatum,  and  the  different  spinal 
nerves. 

'^  Besides  the  different  envelopes  of  the  brain  of  which 
we  have  spoken,  and  the  dura  mater  M^hich  covers  it  in  its 


^  \ 

4 

Hi^^s 

vA-^^-.^ 

\^% 

t^ 

kSj 

i 

■r 

•   ■«rv      *"'*lff] 

W^^ 

Fig.    2.— Francois   Magendie    (1783-1855). 


whole  extent,  this  substance  is  everywhere  surrounded 
with  a  very  fine  serous  membrane  the  principle  use  of 
which  is  to  yield  a  thin  fluid,  which  lubricates  the  brain. 
The  arachnoid  penetrates  to  all  the  cavities  of  the  brain." 
It  is  evident,  therefore,  that  Magendie  knew  not  only  of 
the  existence  and  appearance  of  the  cerebrospinal  fluid,  but 
that  he  was  also  aware  of  the  most  significant  function  of 
the  fluid — namely,  its  protective  nature.  As  soon  as 
Magendie  opened  the  way  for  the  study  of  cerebrospinal 


HISTORY  23 

fluid,  a  number  of  other  investigators  followed  in  his  path. 
Luschka  and  Eckar  studied  the  fluid  from  an  anatomic 
standpoint.  Cavazzani  performed  numerous  experiments 
on  dogs  to  determine  the  physiologic  character  of  the 
cerebrospinal  fluid.  Naunyn  made  a  study  of  the  physics 
of  cerebrospinal  pressure.  Shortly  after,  in  1842,  Lange's 
Anatomy  appeared  and  in  it  were  nine  pages  devoted  ex- 
clusively to  the  discussion  of  cerebrospinal  fluid, — a  dis- 
cussion that  was  both  lucid  and  graphic. 

Almost  sinniltaneously  speculation  began  as  to  tlie  source 
of  cerebrospinal  fluid.  Carl  Schmidt,  in  1850,  expressed 
the  view  that  the  cerebrospinal  fluid  was  not  a  mere  trans- 
udate from  the  blood.  Faivre,  in  1853,  advanced  the  the- 
ory that  the  fluid  was  a  secretion.  Numerous  investiga- 
tions followed  the  promulgation  of  this  idea,  and  hundreds 
of  experiments  were  undertaken  by  anatomists,  patholo- 
gists, physiologists,  and  chemists,  experiments  that  are  be- 
ing carried  on  to  this  very  day. 

AVith  the  discovery  of  a  method  whereby  cerebrospinal 
fluid  could  be  removed  from  the  living  body,  a  new  era  was 
ushered  into  the  history  of  this  fluid.  One  of  the  first 
means  of  obtaining  the  cerebrospinal  fluid  was  by  remov- 
ing it  from  the  skull.  This  operation  was  fraught  wdth 
many  difficulties.  It  involved  the  use  of  a  great  num- 
ber of  instruments  and  necessitated  trephining  of  the  skull 
and  the  making  of  a  scalp  wound. 

A  great  improvement  was  made  on  this  method  in  1855. 
Corning  injected  20  minims  of  a  2  per  cent  solution  of 
hypochlorate  of  cocaine  into  a  space  situated  between  the 
spinous  processes  of  tM'^o  of  the  inferior  dorsal  vertebrae 
of  a  dog.  Five  minutes  after  the  injection  there  were 
marked  evidences  of  incoordination  in  the  posterior  ex- 
tremities. A  few^  minutes  later  there  was  pronounced 
weakness  in  the  hind  legs,  but  there  were  no  signs  of  feeble- 
ness  in   the   anterior   extremities.     The   faradic   current 


24  CEREBROSPIXAL  FLUID 

showed  that  there  was  no  reflex  action  of  the  hind  legs,  but 
the  anterior  extremities  responded  quickly. 

Corning  then  injected  30  niinims  of  a  3  per  cent  solu- 
tion of  cocaine  hypochlorate  between  the  spinous  processes 
of  the  eleventh  and  twelfth  dorsal  vertebrae,  in  a  man  suf- 
fering from  spinal  weakness.  As  there  was  no  numl^ness 
noticeable,  he  injected  30  minims  more  in  the  same  spot 
about  six  or  eight  minutes  later.  In  ten  minutes  the  man 
complained  that  his  legs  felt  "sleepy,"  and  brush  appli- 
cations  showed  that  sensibility  was  greatly  impaired. 

As  a  result  of  his  experiments  Corning  came  to  the 
conclusion  that  local  medication  by  means  of  spinal  punc- 
ture could  prove  of  great  therapeutic  value  in  relieving  a 
number  of  morbid  conditions  of  the  cord.  Unfortunately, 
however.  Corning  left  us  neither  a  description  of  the  tech- 
nic  he  employed  nor  of  the  type  of  needle  he  used.  More- 
over, his  operation  was  attended  Avitli  a  great  degree  of 
risk  in  that  he  introduced  the  needle  too  high  up  in  the 
spinal  colmnn,  thus  incurring  the  danger  of  injury  to  the 
cord. 

In  1891  AV.  Essex  "\Vynter  reported  the  drainage  of  cere- 
brospinal fluid  in  four  cases  of  tuberculous  meningitis.  He 
treated  his  first  case  in  1889,  making  an  incision  in  the  skin 
of  a  patient  suffering  from  tuberculous  meningitis.  In  the 
incision  which  was  made  a  little  to  one  side  of  the  spine  of 
the  second  lumbar  vertebra,  he  introduced  a  Southey  tube 
and  a  trocar.  When  he  felt  that  the  point  of  the  trocar 
had  struck  against  the  lamina,  he  directed  it  slightly  down- 
ward, forced  it  through  the  ligamentum  and  theca,  and  then 
inclined  it  toward  the  median  line.  When  the  trocar  war- 
withdrawn,  clear  fluid  rushed  out  into  the  Southey  tube. 
A  fine,  India-rul)ber  tube  was  then  connected  to  facilitate 
continuous  drainage.  The  symptoms  of  the  disease  sub- 
sided immediately,  although  the  patient  subsequently  died 
from  tuberculous  meningitis.  From  1889  to  1891,  Wynter 
treated  three  more  cases  of  tuberculous  meningitis,  r- 


HISTORY  25 

all  of  them  showed  iiiiproveiuent  for  a  Avhile,  although  they 
subsequently  succumbed  to  the  disease. 

Charles  A.  Morton  (1891)  folloM-ed  the  method  outlined 
^J  Wynter.  In  discussing  the  pathology  of  tuberculous 
meningitis  with  reference  to  its  treatment  by  tapping  the 
spinal  subarachnoid  space,  Morton  says: 

''What  symptoms  can  be  relieved  by  it  only  the  practice 
of  the  operation  can  show ;  that  out  of  four  cases  operated 
on  in  the  Middlesex  Hospital  in  one  there  should  have  been 
contraction  of  the  unduly  dilated  pupils,  and  in  another 
slight  improvement  in  the  general  condition,  is  encourag- 
ing when  we  remember  that  drainage  was  not  maintained 
in  all  the  cases.  The  operation  does  no  harm  and  as  the 
patient  is  already  comatose,  no  anesthetic  is  required." 

Morton,  we  see,  tapped  the  patient  when  he  was  already 
in  comatose  condition.  Although  he  does  not  state  def- 
initely just  what  technic  he  employed,  he  does,  at  the  be- 
ginning of  his  article  speak  of  the  recent  procedure  "of 
tapping  the  subarachnoid  space  of  the  spinal  cord  in  cases 
of  tuberculous  meningitis."  This  would  seem  to  indicate 
that  he  followed  the  method  of  Wynter;  namely  incision  of 
the  skin,  introduction  of  a  trocar  between  the  vertebrae 
and  the  use  of  a  continuous  drain. 

For  the  simplification  and  perfection  of  the  spinal  punc- 
ture w^e  must  turn  to  Quincke.  Corning,  who  w^as  the  first 
to  use  spinal  puncture,  employed  an  operation  that  was 
fraught  with  danger  to  the  cord,  as  the  point  at  which  he 
introduced  the  needle  was  too  high  up  in  the  spinal  canal. 
Wynter,  it  is  true,  did  his  puncture  in  the  lumbar  region, 
but  his  method  necessitated  the  use  of  a  large  trocar,  a 
continuous  drain  and  a  large  incision  in  the  skin.  The 
procedure  of  Quincke  was  a  vast  improvement  over  those 
of  his  predecessors,  both  from  the  standpoint  of  simplicity 
and  of  safety.  Quincke  used  only  a  plain  needle  and  he  so 
perfected  the  technic  of  spinal  puncture  that  there  is  little 
that  can  be  improved  in  his  original  method. 


26 


CEREBROSPIlSrAL  FLUID 


At  the  Tenth  Congress  for  Internal  Medicine,  Quincke 
reported  two  cases  of  hydrocephakis  treated  by  means  of 
withdrawal  of  the  cerebrospinal  fluid.  The  first  was  one 
of  chronic  hydrocephalus  in  which  the  fluid  was  removed 
by  trephining  and  in  which  the  contractures  of  the  extrem- 
ities and  of  the  neck  subsequently  disappeared.  The  sec- 
ond was  that  of  a  child  in  which  lumbar  puncture  resulted 
in  great  improvement.     From  these  and  similar  observa- 


Fig.   3. 


-Drawing   accompanying   original    article   on    lumbar   puncture   by   Quincke,    repre- 
senting lumbar  region  of  skeleton  of  a  one-year-old  child. 


tions  Quincke  concluded  that  spinal  puncture  for  thera- 
peutic purposes  was  indicated  in  marked  cerebral  pres- 
sure, especially  in  cases  of  tuberculous  meningitis  and 
acute  hydrocephalus.  Quincke  not  only  described  the  tech- 
nic  of  spinal  puncture,  but  he  also  measured  the  pressure 
of  the  cerebrospinal  fluid  and  determined  its  chemical  com- 
position so  far  as  he  was  able  wdth  the  chemical  technic 
at  his  command.     (Figs.  3  and  4.) 


HISTORY 


27 


For  two  years  after  Quincke's  experiments  with  spinal 
puncture  no  reports  appeared  in  literature  regarding  its 
use.  It  was  not  until  1893  that  Lichtheim  called  attention 
to  spinal  puncture  as  a  valuable  aid  in  diagnosis,  and  two 
years  later,  in  1895,  Fiibringer  reported  107  punctures  in 
eighty  cases.    In  America,  Browning,  in  1894,  reported  a 


I'ig.   4. — Drawing  accompanying   original   article   on   lumbar   puncture  by   Quincke,    repre- 
senting lumbar  region  of  skeleton  of  a  six-year-old  child. 

series  of  spinal  punctures  and  G.  W.  Jacoby,  in  1895-6,  re- 
ported 30  punctures.  Since  1896  spinal  puncture  has  been 
quite  generally  adopted  as  a  routine  procedure  for  diag- 
nostic and  therapeutic  purposes. 

Bacteriology,  serology,  and  chemistry  have  all  played  an 
important  role  in  shaping  the  history  of  the  cerebrospinal 


28  CEREBKOSPIXAL  FLUID 

fluid.  A  s  for  bacteriology,  there  is  hardly  a  discovery  that 
does  not  bear  a  more  or  less  direct  relation  to  the  history 
of  cerebrospinal  fluid.  The  discovery  of  the  tubercle 
bacillus  b}^  Robert  Koch  changed  the  name  of  acute  hydro- 
cephalus to  tuberculous  meningitis,  and  the  conception  as 
to  its  nature  accordingly.  The  discovery  in  1885  by  Leich- 
tenstern  of  intracellular  diplococci,  later  elaborated  A\dtli 
greater  accuracy  by  Weichselbaum  (1887),  changed  the 
name  of  ** spotted  fever"  and  "epidemic  cephalalgia"  to 
meningococcus  or  epidemic  meningitis,  and  the  discovery 
of  pneumococcus  by  Frankel  and  of  influenza  bacillus  by 
Pfeiffer  did  much  to  clear  up  the  understanding  of 
meningitis  by  introducing  system  where  chaos  previously 
reigned. 

Serology  has  added  a  great  deal  to  the  diagnostic  and 
therapeutic  uses  of  the  cerebrospinal  fluid.  Bordet's  dis- 
covery of  complement  fixation,  Ehrlich's  work  on  inmiu- 
nity  and  Wassermann's  serologic  test  all  found  practical 
applications  in  the  cerebrospinal  fluid.  However,  prob- 
ably the  most  beneficial  contribution  in  the  field  of  serol- 
ogy was  the  discovery  of  antimeningococcic  serum  by  Joch- 
mann,  in  Germany  and  by  Flexner  in  America  and  the  in- 
troduction of  the  intraspinal  injection  of  the  serum  by 
Flexner. 

Chemistry,  too,  has  had  its  share  in  shaping  the  history 
of  the  cerebrospinal  fluid.  It  has  sho\\Ti  us  the  composi- 
tion of  this,  the  clearest  of  liody  fluids,  and  has  shed  light 
on  the  diagnosis  of  meningitis  and  other  affections  of  the 
central  nervous  system. 

Finally,  the  recent  offspring  of  science,  physical  chem- 
istry, is  making  its  impress  also  on  the  history  of  cerebro- 
spinal fluid.  The  H-ion  concentration,  cataphoresis,  the 
Lange  colloidal  gold  tost,  the  ninliydrin  reaction  and  the 
precipitation  tests,  all  of  which  are  based  on  physicochem- 
ical  principles,  have  thrown  light  on  diseases  of  the  central 


HISTORY  29 

nervous  system  in  general  and  on  the  composition  of  body 
fluids  in  particular. 

We  see  that  it  would  hardly  be  an  exaggeration  to  say 
that  the  history  of  cerebrospinal  fluid  in  many  respects  is 
but  a  miniature  history  of  modern  medicine. 

Bibliography 

Contugno:      De    Ischiade    nervosa    Coniiiiciitarius,    Dissertation    <le    Saiulifort, 

17(59,  ii,  411. 
Jour,  (le  physiol.  exper.,  1769,  vii,  S3. 
Corning:      Spinal    Anaesthesia    and    Local    Medication    of    the    Cord,    New 

York  Med.  Jonr.,  1885,  xlii,  483. 
Haller:     Physiologie  des  Men&chen,  1766 

Levinson:     History  of  Cerebrospinal  Fluid,  Am.  Jour.  Syph.,  1918,  ii,  267. 
Longet:     Anatomie  et  Physiologie  due  Systeme  Nerveaux,  1842,  i,  193. 
Magendie:     Memoire  sur  un  liquide  qui  se  trouve  dans  le  crane  et  la  col- 

onne   vertebrale   de   I'liomme   et   des   animaux   niamniiferes,   Compt.   rend. 

Acad.  d.  sc,  Jan.  10,  1825. 
^ragendio:     Recherehes  Physilogiques  et  Cliniques  sur  le  Liquide  Cephalo- 

Raciiidiei!  ou  Cerebrospinal,  Paris,  1842. 
Morton:     The  Pathology  of  Tuberculous  Meningitis  with  Reference  to  i' 

Treatment   by   Tapping   the    Subarachnoid   Space   of   the    Spinal   Cord, 

Brit.  Med.  Jour.,  1891,  ii,  840. 
Quincke :      iJber   Hydrocephalus,   ^'erhandlungen   der   Cong,    f iir   Innere   Med., 

1891,  X,  321, 
Whytt:      Observations  on  the  Dropsv  in  the  Brain,  Woiks  of  Robert  Whytt, 

1768. 
Wy liter:      Four   Cases   of   Tubercular   Meningitis   in   Which    Paracentesis   of 

the  Theca  Vertebralis  was  Performed  for  the  Relief  of  Fluid  Pressure, 

Lancet,  London,  1891,  i,  981. 


CHAPTER  II 

ANATOMY  AND  PHYSIOLOGY  OF  CEREBRO- 
SPINAL FLUID 

LOCATION 

The  brain  and  spinal  cord  are  surrounded  throughout 
their  length  by  a  bed  of  fluid  called  the  cerebrospinal  fluid 
(Liquor  cerebrospinalis,  liquide  cephalorachidien,  Zerebro- 
spinalfliissigkeit).  Besides  the  fluid  that  surrounds  the 
brain  and  cord  there  is  also  a  small  quantity  of  fluid  in  the 
ventricles  of  the  brain. 

The  subarachnoid  space  is  situated  between  the  inner 
vascular  layer  of  the  meninges,  the  pia,  and  the  outer  thin 
layer  of  the  meninges,  the  arachnoid.  It  is  subdivided  into 
numerous  compartments  by  means  of  delicate  trabeculse 
which  run  from  the  pia  to  the  arachnoid.  The  subarachnoid 
space  is  not  of  the  same  depth  everywhere.  In  some 
places  it  is  quite  wide  and  the  trabeculae  are  quite  long, 
whereas  in  others,  especially  over  high  convolutions  of  the 
brain,  the  opposite  is  the  case,  the  space  being  very  small 
and  the  trabecular  very  short.  The  various  wide  spaces  are 
known  bj^  special  terms  suggestive  of  their  form.  Among 
the  most  important  are  the  cisterna  magna,  M^hich  is  lo- 
cated between  the  under  surface  of  the  cerebellum  and  the 
medulla;  the  cisterna  pontis  which  is  the  continuation  of 
the  subarachnoid  space  of  the  spinal  cord  upwards  to  the 
floor  of  the  cranium ;  and  the  cisterna  hasalis  which  is  sit- 
uated in  front  of  the  pons.  The  subarachnoid  space  of  the 
cord,  like  that  of  the  brain,  is  subdivided  by  trabecular,  or 
septa,  and  is  also  quite  wide. 

In  addition  to  the  fluid  contained  in  the  subarachnoid 
space  of  the  brain   and  cord   there  is   fluid  in  the  ven- 

30 


Fig.   5. — Section    of   Ininian   brain   showing  the   chorioid    plexus,   the  extent,    relations,    and 
intercommunications  of  the  brain   ventricles   (See   Fig.   6.) 


ANATOMY   AND   PHYSIOLOGY  31 

tricles  of  the  brain:  the  two  lateral,  the  third,  the  fourth, 
and  the  fifth  ventricles  (Figs.  5  and  6). 

Lining  the  ventricles  there  is  a  tuft  of  blood  vessels,  cov- 
ered by  a  single  layer  of  epithelium  called  the  chorioid 
plexus  (Figs.  5,  6  and  7).  This  plexus  is  an  ingrowi;h  or 
folding  of  the  pia,  the  layer  of  the  meninges  immediately 
adjacent  to  the  brain. 

Two-thirds  of  the  blood  supply  of  the  plexus  in  man  is 
furnished  by  the  anterior  chorioid  branch  of  the  internal 
carotid  artery  which  enters  the  plexus  at  the  anterior  end 
of  the  descending  cornu.  The  remainder  is  supplied  by  the 
posterolateral  chorioid  arter}^,  a  branch  of  the  posterior 
cerebral.  These  arteries  break  up  into  arterioles,  the  larg- 
est of  which  are  visible  to  the  naked  eye.  After  passing 
through  the  network  of  capillaries,  the  blood  returns 
through  the  chorioid  vein  to  the  internal  cerebral  veins 
where  it  joins  its  fellow^  and  forms  the  cerebral  vein,  or  vein 
of  CJalen. 

The  walls  of  the  blood  vessels  of  the  chorioid  plexus, 
measure,  in  some  tufts,  0.2  mm.  in  thickness,  while  in  oth- 
ers they  form  only  a  thin  membrane  between  the  lumen  and 
cuboidal  cells  on  the  surface.  Much  variation  exists  also 
in  the  size  of  the  lumina. 

Sundwall  divides  the  vessels  of  the  chorioid  plexus  into 
two  groups:  (1)  The  vessels  with  thick  walls,  which  as  a 
rule,  possess  narrow  lumina  and  have  the  same  general 
structure  as  the  small  arteries.  AVeigert's  stain  shows  a 
well-developed  internal  elastic  layer,  which  in  most  in- 
stances is  corrugated.  In  the  media,  which  is  quite  well 
developed,  fine,  wavy,  elastic  fibers  may  be  seen.  The 
fibers  may  be  traced  to  the  cuboidal  cells  for  which  they 
frequently  form  a  basic  membrane.  (2)  The  second  group 
of  vessels  are  those  with  comparatively  thin  walls  and 
wade  lumina.  These  may  be  regarded  as  veins  or  sinuses. 
No  muscular  tissue  can  be  made  out  in  the  walls  of  this 
second  group,  the  walls  being  composed  almost  entirely  of 


32 


CEREBROSPIXAL  FLUID 


S.  PEL 


COR. ANT. 


coR.Tosr. 


v.m 

TLXOKV-'m 


AN.  CENT. 


Fig.  6. — A  diagram  of  Fig.  5.  The  ventricles  are  deeply  shaded.  The  outlines  of  the 
ventricles  which  appear  in  Fig.  5  are  indicated  by  continuous  lines.  On  the  right  side 
the  position  of  the  underlying  ventricular  cavities  is  also  indicated  by  shading,  hut  the 
outline  is  a  broken  line. 

S.  PEL.,   Septum  pellucidum. 
F.  M.,  Foramen  of  Monro. 
y.   III.,   Third   ventricle. 
N.  L.,   Lentiform  nucleus. 
C.  I.,  Internal  capsule. 

COR.  INF.,   Inferior  horn   of  lateral   ventricle. 
THAL..   Optic   thalamus. 
HIP.,  Hippocampus. 
FIM.,  Fimbria. 

PL.  COR.,  Lateral  chorioid  plexus. 
COR.  POST.,   Posterior  horn  of  lateral  ventricle. 
v.  IV.,   Fourth  ventricle. 

PL.   COR.    v.  IV.,    Reflected   chorioid   plexus  of  fourth   ventricle. 
CAN.  CENT.,  Position  of  central  canal. 

COR.  ANT.,  Position  of  anterior  horn  of  lateral  ventricle. 
N.    CAUD.,    Caudate   nucleus. 
S.   C,   Fissure   of   Rolando    (central   sulcus). 
FX.,  Fornix   cut  through  at   column  of  the  fornix. 
PL.   COR.,  LAT.,   Lateral  chorioid   plexus. 
PL.    COR.    V.    III.,    Reflected    chorioid    plexus    of    third    ventricle    and    septum    inter- 

positum. 
COR.  INF.,   Position   of  the  inferior   horn   of  lateral  ventricle. 
GL.  P.,  Left  half  of  pineal  body. 
AQ.   SYL.,   Aqueduct   of   Sylvius. 

COR.    POST^,    Position    of   posterior    horn    of    lateral    ventricle. 
PO.   CBL.,   Cut   surface    of   cerebellar   peduncles. 
R.   L.    V.   IV.,    Lateral   recess   of  fourth   ventricle. 


ANATOMY   AND   PHYSIOlOGV 


83 


white  fibrous  comieetive  tissue  and  are  so  similar  through- 
out in  their  structure  that  they  can  not  be  differentiated 
into  intima,  media,  and  adventitia.  Only  here  and  there 
may  be  seen  a  few  fine  elastic  fibers. 

The  walls  contain  numerous  small  vessels  and  capillaries 
(vasa  vasorum)  of  varying  caliber.  They  are  rich  also  in 
nuclear  elements,  such  as  endothelial  cells,  connective- 
tissue  cells  and  interstitial  granule  cells. 

The  cerebrospinal  fluid  in  one  ventricle  of  the  brain  com- 
municates directly  with  the  fluid  in  the  other  ventricles 


Fig.   7. — Photograph   of  a   chorioid   plexus   detached    from    the  ventricles. 

through  the  various  openings  connecting  them.  The  only 
exception  to  this  rule  is  the  fifth  ventricle  which  contains 
very  little  or  no  fluid.  Thus,  the  fluid  in  the  lateral  ven- 
tricles flows  into  the  third  through  the  foramen  of  Monro, 
and  the  fluid  in  the  third  communicates  with  that  in  the 
fourth  by  means  of  the  aqueduct  of  Sylvius.  (Figs.  5 
and  6.) 

The  cerebrospinal  fluid  of  the  subarachnoid  space  com- 
municates with  the  fluid  in  the  ventricles  of  the  brain 
through  the  foramen  of  Magendie  which  opens  into  the 


34  CEREBROSPIXAL  FLI'ID 

posterior  part  of  the  fourth  ventricle  and  through  the 
foramina  of  Lusehka  and  numerous  other  apertures  which 
open  into  the  lateral  ventricles.  Some  authors,  notably 
Schmorl,  claim  that  no  communication  exists  between  the 
cerebrospinal  fluid  in  the  ventricles  of  the  brain  and  the 
fluid  in  the  subarachnoid  spaces  of  the  brain  and  cord. 
They  base  this  claim  on  two  observations:  (1)  the  finding 
of  bile  in  cases  of  icterus  in  the  cerebrospinal  fluid  of  the 
cord,  but  not  in  the  fluid  of  the  ventricles;  (2)  by  Schmorl 's 
finding  of  a  positive  Nonne-Apelt  reaction  in  the  cerebro- 
spinal fluid  of  the  cord  and  a  negative  reaction  in  the  fluid 
of  the  ventricles. 

My  own  observations  do  not  bear  out  the  conclusion  of 
Schmorl.  I  examined  both  the  spinal  and  ventricular  fluid 
in  cases  of  meningitis  and  fomid  them  quite  alike  in  both 
their  globulin  and  bacterial  content.  In  fact,  in  my  cases, 
the  ventricular  fluid  at  times  gave  much  stronger  globulin 
reactions  than  did  the  fluid  from  the  spinal  canal.  How- 
ever, the  best  evidence  that  a  communication  exists  be- 
tween the  ventricles  of  the  brain  and  the  subarachnoid 
spaces  is  the  commonly  observed  fact  that  in  hemorrhages 
into  the  ventricles  the  fluid  obtained  by  lumbar  puncture 
contains  coagulated  blood.  It  is  also  well  knoMm  that  when 
a  colored  fluid  is  injected  into  the  ventricles,  it  can  be  re- 
covered by  lumbar  puncture  in  a  few  minutes.  Vice  versa, 
if  the  colored  fluid  is  injected  between  the  atlas  and  axis 
it  can  be  recovered  from  the  lateral  ventricle.  It  is  also 
well  kno^^^l  that  a  tense  fontanelle  will  go  down  with  the 
withdrawal  of  cerebrospinal  fluid  by  lumbar  puncture.  All 
this  points  to  a  direct  communication  between  the  ven- 
tricles of  the  brain  and  the  subarachnoid  space. 

FORMATION  AND  ABSORPTION 

The  rate  of  formation  of  cerebrospinal  fluid  is  still  a 
matter  of  conjecture.     Falkenheim  and  Xaunyn  observed 


AiSTATOMY    AND    PHYSIOLOGY  35 

that  from  1  e.c.  in  six  minutes  to  1  c.c.  in  forty  minutes 
flowed  ont  of  a  cannula  introduced  into  the  subarachnoid 
space  of  a  dog-.  In  another  dog,  weighing  23  kilos,  they 
observed  as  large  a  flow  as  240  c.c.  of  fluid  in  twenty-four 
hours  and  in  still  another  dog,  weighing  20  kilos,  they  re- 
ported a  flow  of  36  c.c.  in  twenty-four  hours.  According 
to  these  experiments  there  does  not  seem  to  be  any  rela- 
tion between  body  weight  and  the  rate  of  formation  of 
cerebrospinal  fluid  nor  between  the  rate  of  formation  and 
the  arterial  pressure.  In  the  numerous  reports  of  cases  of 
cerebrospinal  rhinorrhea,  the  amount  of  fluid  flowing  out 
from  the  nose  varied  from  96  c.c.  to  720  c.c.  per  day.  Til- 
laux,  for  instance,  reports  a  case  in  wiiich  there  w^as  com- 
munication between  the  subarachnoid  space  and  the  dura 
and  in  which  the  daily  flow  of  cerebrospinal  fluid  from  the 
nose  averaged  one-fourth  of  a  liter.  Wallace  MacKenzie 
reports  a  case  of  cerebrospinal  rhinorrhea  where  the  aver- 
age flow  of  fluid  per  hour  w^as  one  ounce,  making  a  total 
of  720  c.c.  in  a  day.  In  trauma  of  the  spinal  column  even 
greater  amounts  of  fluid  have  been  observed,  as  in  the  case 
of  Giss  in  which  there  was  a  flow  of  fluid  measuring  frojn 
one  and  one-half  to  two  liters.  It  seems  likely,  however, 
that  the  large  amounts  of  cerebrospinal  fluid  observed  in 
cases  of  trauma  are  no  indication  of  the  normal  rate  of 
formation  in  cerebrospinal  fluid,  as  it  is  well  known  that 
whenever  there  is  irritation  of  a  serous  membrane  there 
is  an  increase  of  the  fluid  in  the  cavity. 

So  far  as  we  know,  no  one  has  as  yet  determined  the  rate 
of  formation  of  cerebrospinal  fluid  under  normal  condi- 
tions. One  point,  however,  has  been  quite  definitely  es- 
tablished by  Falkenheim  and  Naunyn  and  that  is  that  there 
is  a  constant  secretion  and  absorption  of  the  fluid. 

That  the  cerebrospinal  fluid  has  a  circulation  has  been 
shown  by  Magendie,  but  the  mode  of  circulation  has  not 
been  entirely  established.  It  is  thought  that  the  fluid 
starts  in  the  ventricles  of  the  brain,  that  it  passes  through 


36  CEEEBROSPIXAL  FLUID 

the  foramina  of  Magendie  and  Lusclika  into  the  subarach- 
noid space  of  the  brain,  then  doAxiiAvard  along  the  posterior 
aspect  of  the  spinal  cord.  On  reaching  the  end  of  the  cord 
the  fluid  passes  upward  along  the  anterior  surface  of  the 
cord.  Some  of  the  fluid  is  absorbed  there.  The  rest 
spreads  over  the  convexities  of  the  hemispheres  from 
whence  it  is  absorbed. 

The  data  on  the  absorption  of  the  cerebrospinal  fluid  are 
not  numerous.  Duret  was  able  to  introduce  583  c.c.  of  wa- 
ter into  the  subarachnoid  of  a  dog  in  the  course  of  two 
hours.  Naunyn  and  Schreiber  introduced  400  c.c.  of  phys- 
iologic salt  solution  into  the  subarachnoid  space  of  a  dog, 
weighing  9i/^  kilograms,  in  the  course  of  an  hour  and  three 
quarters,  using  100  mm.  mercury  pressure  for  the  injec- 
tion. Falkenheim  and  Naunyn  showed  that  the  absorption 
is  rapid  even  when  the  fluid  is  injected  wdth  a  very  little 
force.  Dandy  and  Blackfan  injected  1  c.c.  of  phenolsul- 
phonephthalein  into  a  dog  after  withdrawing  1  c.c.  of  cere- 
brospinal fluid.  The}'  examined  the  quantity  of  phenolsul- 
phonephthalein  excreted  in  the  urine  by  a  colorimetric 
method,  and  found  that  in  the  first  hour  after  the  injection 
there  were  16.6  per  cent  of  phenolsulphonephthalein  ex- 
creted in  the  urine;  in  the  second,  17.8  per  cent;  in  the 
third,  13.6 ;  in  the  fourth,  7.2  per  cent ;  in  the  fifth,  4.5  per 
cent;  in  the  sixth,  2.2  per  cent;  in  the  seventh,  1.3  per  cent; 
and  in  the  eighth,  1.3  per  cent.  From  these  experiments 
they  concluded  that  the  absorption  of  the  cerebrospinal 
fluid  is  fairly  regular  for  a  period  of  from  three  to  four 
hours,  and  that  it  diminishes  progressively  after  this  time. 
They  set  a  minimum  of  four  to  six  hours  for  the  comple- 
tion of  absorption  of  the  fluid,  making  four  to  six  renew- 
als in  24  hours. 

The  above,  however,  can  not  be  taken  as  an  index  for 
the  rate  of  absorption  of  the  cerebrospinal  fluid,  as  phenol- 
phthalein  is  a  foreign  substance,  and,  as  is  well  knowTi,  a 
foreign  substance  is  rapidly  eliminated  from  the  body. 


ANATOMY   AND   PHYSIOLOGY  37 

witlioiit  reference  to  the  absorption  power  of  the  body 
fluids.  One,  for  instance,  is  not  justified  in  saying  that 
since  60  per  cent  of  a  dye  is  excreted  in  the  urine  in  two 
hours  by  the  kidnej^  60  per  cent  of  the  water  of  the  blood 
is  excreted  in  two  liours.  Foreign  substances  are  elim- 
inated by  a  special  mechanism  and  bear  no  relation  to  the 
absorption  of  the  body  fluids. 

So  far  the  rate  of  absorption  of  cerebrospinal  fluid  has 
not  been  determined,  and  we  believe  will  not  be  deter- 
mined so  long  as  the  rate  of  formation  of  the  fluid  is  not 
known,  for  the  rate  of  absorption  naturally  depends  on 
the  rate  of  formation. 

As  for  the  channel  through  which  absorption  of  the 
cerebrospinal  fluid  takes  place,  there  is  a  divergence  of 
opinion.  Mott  considers  the  perivascular  lymphatics  as 
the  channel  of  absorption.  It  has  been  proved  by  others, 
also,  that  a  portion  of  the  fluid  is  drained  by  the  lymphat- 
ics into  the  deep  cervical  glands,  and  that  a  small  portion 
flows  into  the  lymph  vessels  of  the  nose,  the  perilymph 
spaces  of  the  labyrinth  of  the  ear  and  in  the  perineural 
sheets.  This  is  somewhat  substantiated  by  the  cases  of 
cerebrospinal  rhinorrhea  reported  in  the  literature.  It 
has  been  found,  however,  that  normally  the  absorption  by 
way  of  the  lymphatic  system  removes  only  a  very  small 
quantity  of  the  fluid.  Hill,  Ziegler,  and  Spina  showed  that 
methjd  blue  injected  into  the  subarachnoid  space  can  be 
recovered  from  the  stomach  in  twenty  minutes,  while  it 
takes  hours  before  the  lymphatics  of  the  neck  are  discol- 
ored by  the  stain.  Dandy  and  Blackfan  introduced  a  can- 
nula into  the  thoracic  duct  after  they  had  injected  phenol- 
sulphonephthalein  into  the  subarachnoid  space  and  found 
that  there  was  ver>^  little  absorption  by  the  lymph,  com- 
pared with  that  by  the  blood. 

These  and  many  other  experiments  indicate  that  the 
greatest  amount  of  cerebrospinal  fluid  is  absorbed  into  the 
blood  stream  proper.     According  to  Schwalbe,  Key  and 


38  CEHEBllOSPIXAL  FLUID 

Betzius,  the  Pacchionian  bodies  perform  the  function  of 
absorbing  the  fluid,  but  according  to  recent  studies  these 
bodies  are  concerned  only  little  in  this  absorption.  Bohn, 
Reiner  and  Schnitzler  advocate  the  idea  that  the  fluid  is 
absorbed  by  the  stomata  of  the  meninges.  This  theory, 
however,  has  no  real  foundation,  and  at  present  the  weight 
of  evidence  is  in  favor  of  the  absorption  of  the  cerebro- 
spinal fluid  by  a  process  of  dilTusion  into  the  blood  from 
the  subarachnoid  space  of  the  brain,  and  particularly  of 
the  cord. 

PERMEABILITY 

It  is  conceded  by  most  observers  that  under  normal  con- 
ditions no  foreign  substances,  or  at  least  very  few,  pass 
from  the  blood  into  the  cerebrospinal  fluid.  This  resist- 
ance of  the  meninges  to  the  entrance  of  a  foreign  substance 
is  held  to  be  due  to  the  impermeability  of  the  meninges, 
although,  if  we  accept  the  view  that  the  cerebrospinal  fluid 
is  secreted  by  the  chorioid  plexus  we  should  speak  rather 
of  the  impermeability  of  the  chorioid  plexus.  Various  ex- 
periments have  been  made  to  demonstrate  this  property  of 
the  chorioid. 

Cavazzani  injected  potassium  iodide  into  dogs  intraperi- 
toneally  and  recovered  only  very  small  amounts  of  it  in  the 
cerebrospinal  fluid.  Sicard,  Lewandowsky,  and  Rotky 
repeated  the  experiment  and  could  not  detect  potassium 
iodide  in  the  cerebrospinal  fluid  at  all.  Lewandowsky 
found  that  a  few  centigrams  of  sodium  ferrocyanide  in- 
jected into  subarachnoid  space  rapidly  produced  toxic 
symptoms  while  four  to  six  grams  injected  into  the  jugular 
vein  in  rabbits  of  the  same  weight  produced  no  specific 
symptoms.  This  could  not  have  been  attributed  to  the  so- 
lution employed,  for  a  10  per  cent  salt  solution  injected 
into  the  subarachnoid  space  produced  only  slight  effects. 
Lewandowsky  was  also  able  to  show  the  transmissibility  of 
only  very  small  traces  of  strychnine  in  the  cerebrospinal 


ANATOMY    AND    PHYSIOLOGY  39 

fluid  ol'  animals,  but  none  in  man.  Von  Jaksch  and  Sicard 
could  not  detect  the  presence  of  mercuric  salts  after  inunc- 
tion into  the  skin.  Livon  and  Bernard  could  detect  sal- 
icylates, but  in  very  small  amounts,  in  the  cerebrospinal 
fluid  of  a  dog  after  intravenous  injection. 

Antitoxin  also  passes  over  into  the  cerebrospinal  fluid 
only  in  traces.  Behring;  injected  hens  l)oth  subcutaneously 
and  intravenously  with  tetanus  toxin  and  found  that  they 
suffered  no  ill  effects.  However,  when  he  injected  the 
same  amount  of  toxin  into  the  subdural  space  the  hens 
died  from  typical  tetanus. 

Mestrezat  found  that  when  sodium  nitrate  is  adminis- 
tered to  a  normal  individual  before  a  spinal  puncture  is 
made,  the  fluid  shows  very  little  or  no  nitrate,  w^hile  in 
cases  of  meningitis,  the  drug  is  present  in  large  quantities. 

There  are  a  few  chemical  substances,  however,  that  do 
seem  to  be  transmitted  from  the  blood  into  the  cerebro- 
spinal fluid,  namely,  hexamethylamine,  alcohol  and  chloro- 
form. Hexamethylamine  has  been  shown  by  Crowe,  Hold 
and  Ratsky  to  be  present  in  the  cerebrospinal  fluid  of 
both  man  and  animal  after  administration  by  mouth.  This 
observation  has  led  to  the  suggestion  of  giving  hexamethy- 
lamine in  meningitis  and  poliomyelitis.  Alcohol  was  shown 
by  Schottniiiller  and  Sclmnun  to  accumulate  in  the  cerebro- 
spinal fluid  in  even  larger  amounts  tlian  in  the  blood. 

Of  pathologic  products,  acetone,  acetoacetic  acid,  lactic 
acid  and  bile  have  been  found  to  pass  over  into  the  cere- 
l)rospinal  fluid  quite  readily  even  when  the  meninges 
were  not  affected.  I  found  the  chloridc^s  in  the  fluid  to  be 
increased  in  nephritis  and  the  sugar  to  be  increased  in 
diabetes. 

Some  of  the  experiments  on  the  impermeability  of  the 
meninges  and  chorioid  plexus  are  not  entirely  convincing 
because  they  deal  with  negative  evidence.  Very  fre- 
quently also  the  technic  and  method  have  been  at  fault. 
It  is  certain,  however,  that  there  is  a  vast  difference  be- 


40  CEREBROSPINAL  FLUID 

tween  the  transmissibility  of  chemical  and  immune  snli- 
stances  in  health  and  in  disease  and  although  we  may 
not  know  positively  whether  the  meninges  or  chorioid  plexus 
are  entirely  impermeable  in  health,  we  do  know  that  they 
become  permeable  in  disease — a  fact  of  great  importance 
in  the  genesis  and  also  in  the  diagnosis  and  treatment  of 
the  diseases  of  the  meninges. 

FUNCTION 

That  the  cerebrospinal  fluid  has  a  mechanic  function 
there  is  no  doubt.  The  fluid  forms  a  water  bed  around  the 
cord  and  brain  and  thus  prevents  the  jarring  from  external 
trauma.  The  fluid  also  equalizes  the  pressure  between  the 
brain  and  the  cord.  Magendie,  many  years  ago,  pointed  out 
the  following: 

''The  cerebrospinal  fluid  which  is  barely  mentioned  in 
the  classical  works,  not  only  fills  out  the  empty  spaces  in 
the  skull  and  spinal  canal,  it  has  a  greater  function,  mainly 
to  exert  a  continual  and  regulated  pressure  on  the  neuron 
masses." 

However,  a  number  of  other  functions  are  ascribed  to 
cerebrospinal  fluid.  Mott  believes  that  it  is  the  function  of 
the  fluid  to  give  up  carbon  dioxide  and  water  to  the  blood 
and  to  take  up  oxj^gen  and  sugar.  Gushing,  and  later  Fra- 
zier,  suggested  that  the  fluid  may  be  the  medium  of  dis- 
tribution of  the  active  principle  of  the  pituitary  to  the 
tissues  of  the  central  nervous  system,  which  is  essential 
to  metabolism.  Halliburton  considers  the  fluid  as  a  Locke 
modification  of  Ringer's  solution.  The  sugar,  as  in 
Locke's  solution,  serves  to  supply  the  energy,  the  protein 
serves  to  repair  the  wear  and  tear  resulting  from  the  ac- 
tion of  the  nervous  system,  and  the  fluid  as  a  whole  acts 
as  an  ideal,  physiologic  salt  solution  bathing  the  neurones 
and  maintaining  their  osmotic  equilibrium. 

According  to  Gaskel  the  neural  tube  is  a  primitive  di- 
gestive canal,  and  the  cerebrospinal  fluid  a  primitive  gas- 


ANATOMY   AIs^D   PHYSIOLOGY  41 

trie  juice.  Dandy  calls  attention  to  the  gill-like  appear- 
ance of  the  chorioid  plexus,  a  fact  that  inclines  him  to  be- 
lieve that  the  chorioid  plexus  and  the  cerebrospinal  fluid 
are  concerned  in  respiration,  Pettit  and  Girard  hold  that 
the  fluid  has  an  internal  secretion.  Still  another  theory 
of  recent  origin  voices  the  opinion  that  the  fluid  serves  as 
a  destroyer  of  toxic  substances  introduced  into  the  cere- 
brospinal nervous  system. 

Of  the  various  theories  advanced  in  regard  to  the  func- 
tion of  the  cerebrospinal  fluid  that  of  mechanic  function 
has  an  unquestionable  basis.  All  the  other  theories  are 
open  to  objection  of  one  kind  or  another;  they  lack  in  suf- 
ficient evidence.  Mott's  theory  that  the  cerebrospinal 
fluids  gives  up  CO2  and  water  to  the  blood  seems  illogical 
since  the  circulation  of  the  fluid  is  entirely  too  slow  and 
therefore  inadequate  to  carry  CO2  to  the  blood.  Fra- 
zier's  suggestion  needs  further  confirmatory  evidence. 
The  theories  of  Dandy  and  of  Gaskel  do  not  appear  at  all 
plausible.  As  to  the  theory  that  the  fluid  destroys  toxin, 
the  objection  may  be  raised  that  very  few  toxins  are  able 
to  get  into  the  cerebrospinal  canal  under  normal  condi- 
tions, as  shown  in  the  discussion  on  permeability.  Of  all 
the  theories,  the  only  one  that  has  a  firm  basis  is  that  of 
mechanical  function. 

ORIGIN 

The  question  of  the  origin  of  cerebrospinal  fluid  is  one 
that  has  engaged  the  attention  of  many  physiologists  and 
chemists,  and  even  today  the  problem  is  far  from  settled, 
although  attempts  have  been  made  to  solve  it  through  the 
aid  of  histology,  chemistry,  physiology,  and  pathology. 

Carl  Schmidt  (1850)  was  the  first  to  voice  the  opinion  that 
cerebrospinal  fluid  w^as  a  secretion  and  not  a  transudate  by 
virtue  of  the  difference  in  the  chemical  composition  of  the 
blood  and  the  fluid.  Faivre  (1854)  also  spoke  of  the  inti- 
mate relation  between  the  fluid  and  the  chorioid  plexus. 


42  CEREBROSPINAL  FLUID 

Luselika,  Schlaepfer,  Yoshimura,  Ernst,  Kafka,  Mott  and 
Meek  found  the  existence  of  vacuoles  in  the  chorioid 
plexus,  and  all,  with  the  exception  of  Meek,  connected  the 
globules  with  the  secretion  of  cerebrospinal  fluid.  Mott 
examined  the  chorioid  plexus  of  human  beings  soon  after 
death  and  on  staining  with  methylene  blue,  he  found  the 
cells  of  the  chorioid  plexus  to  contain  many  vacuoles. 
This,  he  believed,  proved  conclusively  that  the  chorioid 
cells  secreted  some  substance.  He  compared  the  epithelial 
cells  of  the  chorioid  with  those  of  the  lacrymal  glands. 

Physiologic  evidence  as  to  the  secretion  of  the  chorioid 
plexus  was  also  brought  forth  by  many  observers.  Kafka 
found  that,  after  an  injection  of  pilocarpine,  the  epithelial 
globules  of  the  chorioid  plexus  were  multiplied.  Cavaz- 
zani  showed  that  lymphagogues  did  not  affect  the  cerebro- 
spinal fluid.  His  observation  that  the  alkalinity  of  cere- 
brospinal fluid  was  considerably  less  than  that  of  the 
blood  also  led  him  to  the  conclusion  that  cerebrospinal 
fluid  was  a  secretion.  Cappelleti  came  to  the  same  conclu- 
sion regarding  the  origin  of  the  cerebrospinal  fluid.  He 
found  that  ethyl  ether  and  pilocarpine  increased  the  flow 
of  the  fluid,  whereas  atropin  and  hyoscyamin  retarded  the 
flow.  Pettit  and  Girard  found  that  the  administration  of 
pilocarpine,  muscarin  and  ether  to  animals  produced  a 
marked  increase  in  the  secretion  of  the  plexus.  Dixon  and 
Halliburton  brought  about  an  increase  in  the  flow  of  the 
fluid  by  injecting  chorioid  extract.  They  claim  that  the 
chorioid  plexus  contains  a  hormone  which  when  liberated 
into  the  blood  becomes  the  precursor  and  regulating  me- 
dium of  the  secretory  activitj^  of  the  plexus. 

Interesting  contributions  to  the  chemical  phase  of  the 
problem  have  been  made  by  Schmidt,  Polanyi,  Schottmiiller 
and  Schumm.  The  work  of  Schmidt  has  been  mentioned. 
Polanyi  concluded,  from  the  small  protein  content  and  the 
high  molecular  concentration  of  fluid  in  cases  of  hydro- 
cephalus, that  the  fluid  is  not  a  transudate.    Schottmiiller 


ANATOMY    AND    PHYSIOLOGY  43 

and  Scliiuiiiii  claiiiied  that  tlie  liuid  is  not  subordinate  to 
the  blood,  as  they  had  found  the  fluid  in  some  cases  to  con- 
tain alcoliol  in  as  great  and  greater  quantities  than  the 
blood.  Leopold  and  Bernhard  subscribe  to  the  view  of 
Gushing  that  the  cerebrospinal  fluid  is  secreted  by  the 
chorioid  plexus  on  the  ground  that  they  were  unable  to  find 
uric  acid  in  the  fluid  in  normal  individuals. 

Evidence  from  pathologic  conditions,  as  to  the  secretive 
powers  of  the  chorioid  plexus  has  been  furnished  by  other 
observers.  Charles  and  Levy  report  a  case  of  hydroceph- 
alus in  which  there  was  hypertrophy  of  the  chorioid  plexus. 
Dandy  and  Blackfan  occluded  the  aqueduct  of  Sylvius  by 
a  gelatine  capsule  and  produced  thereby  an  internal  hydro- 
cephalus. This  would  tend  to  show  that  the  fluid  is  se- 
creted above  the  aqueduct  and  most  likely  by  the  chorioid 
plexus.  That  part  of  the  fluid  might  come  from  the  ven- 
tricles themselves  the  work  of  Francini  would  indicate, 
as  he  noticed  secretory  phenomena  of  the  ependyma  cells 
of  the  ventricles  after  ether  injections. 

On  the  other  hand,  there  are  observations  that  would 
tend  to  show  that  cerebrospinal  fluid  is  not  a  secretion. 
Mestrezat,  on  the  basis  of  chemical  analysis  of  the  blood 
plasma  and  the  cerebrospinal  fluid,  concluded  that  the  fluid 
is  not  a  filtrate,  a  transudate,  or  a  secretion,  but  a  dialy- 
sate  of  blood  plasma  produced  by  a  passage  through  special 
epithelial  cells.  McClendon,  on  physico-chemical  ground, 
claimed  that  the  cerebrospinal  fluid  was  an  ultrafiltrate. 

From  the  various  data  presented,  one  would  be  inclined 
to  believe  that  the  chorioid  plexus  is  the  seat  of  the  origin 
of  the  cerebrospinal  fluid.  It  is  quite  plausible  to  assume 
tliat  the  ])loxus  is  located  in  the  ventricles  for  some  purpose 
and  most  likely  for  the  secretion  of  the  cerebrospinal  fluid. 
Yet  the  evidence  brought  forward  to  prove  these  points  is 
not  altogether  convincing. 

Mott's  observation  of  the  existence  of  vacuoles  in  the 
chorioid  plexus,  an  observation  that  has  been  corroborated 


44  CEREBROSPINAL  FLUID 

by  Lusclika,  Findlay  and  Galeotti,  does  not  necessarily 
indicate  that  the  cliorioid  plexus  secretes  cerebrospinal 
fluid.  Meek  believes  that  the  vacuoles  are  due  to  the  melt- 
ing of  the  fat  in  the  epithelial  cells  of  the  chorioid  through 
the  action  of  such  hardening  fluids  as  alcohol  and  xylol, 
for  chorioid  cells  which  have  not  been  subjected  to  alco- 
hol and  xylol  do  not  show  vacuoles.  Pettit  and  Girard  be- 
lieve that  these  vacuoles  are  due  to  mechanical  injury 
and  to  postmortem  changes.  Becht  argues  that  secreting 
cells  should  not  show  vacuoles  at  all,  but  should  be  smaller 
than  ordinary  cells.  He  points  out  the  fact  that  secreting 
cells  in  the  parotid  and  other  glands  become  smaller  dur- 
ing the  period  of  activity,  whereas  those  of  the  chorioid 
plexus  become  larger.  He  notes  other  differences  as  well. 
While,  in  most  glands,  during  the  period  of  activity  the 
cytoplasm  is  differentiated  into  an  inner  granular  layer 
and  an  outer  clear  zone  with  well-defined  nuclei,  in  the 
chorioid  plexus,  during  activity,  the  very  opposite  takes 
place.  The  cytoplasm  becomes  differentiated  into  an  inner 
clear  and  an  outer  granular  zone  and  the  nucleus  can  hardy 
be  distinguished  from  the  nucleus  of  the  resting  cells, 

Cavazzani's  evidence  regarding  the  alkalinity  of  the 
cerebrospinal  fluid  does  not  hold  good,  because  the  methods 
used  for  the  determination  of  the  alkalinity  were  not  the 
proper  ones,  and  vnth  newer  methods,  the  acidity  of  the 
fluid  is  the  same  as  that  of  the  blood.  As  for  the  effect  of 
pilocarpine  in  increasing  the  amount  of  cerebrospinal  fluid, 
this  does  not  necessarily  show  that  the  fluid  is  a  secretion. 
The  increase  in  the  secretion  can  just  as  readily  be  attrib- 
uted to  the  action  of  the  drug  on  the  blood  vessels. 

As  for  the  chemical  evidence  brought  forth  by  Polanyi, 
is  it  not  plausible  to  assume  that  the  cerebrospinal  fluid 
may  come  from  the  blood,  and  that  the  smaller  content  of 
protein  in  the  fluid  be  due  to  the  changes  the  fluid  under- 
goes during  the  process  of  filtration?  Sehottmiiller's  ob- 
servation that  there  may  be  a  greater  amount  of  alcohol  in 


ANATOMY   AND   PHYSIOLOGY  45 

the  cerebrospinal  fluid  than  in  the  blood  may  be  explained 
on  the  ground  of  slower  absorption  in  the  cerebrospinal 
canal  than  in  the  blood. 

Until  it  is  possible  to  remove  the  chorioid  we  shall  not 
know  conclusively  whether  the  chorioid  is  the  seat  of  the 
secretion  of  the  cerebrospinal  fluid.  All  that  we  can  say 
at  present  with  any  degree  of  certainty  is  that  there  is  con- 
vincing proof  to  show  that  the  cerebrospinal  fluid  is  pro- 
duced above  the  aqueduct  of  Sylvius. 

The  fact  that  nearly  all  constituents  of  the  blood  are 
present  in  the  cerebrospinal  fluid,  and  that  the  physico- 
chemical  properties  of  the  cerebrospinal  fluid  are  practi- 
cally the  same  as  that  of  the  blood,  would  make  one  believe 
that  the  cerebrospinal  fluid  is  a  direct  product  of  the  blood, 
most  likely  separated  out  by  the  chorioid  plexus. 

The  data  presented  in  this  chapter  may  be  summarized 
in  the  following  points: 

1.  The  cerebrospinal  fluid  is  contained  in  the  subarach- 
noid space  of  the  brain  and  cord. 

2.  The  fluid  in  the  various  ventricles  is  in  direct  com- 
munication with  each  other  and  with  the  fluid  of  the  cord. 

3.  The  cerebrospinal  fluid  has  a  circulation. 

4.  The  rate  of  formations  of  normal  fluids  is  unknown. 
So  is  the  rate  of  absorption. 

5.  Absorption  seemingly  takes  place  by  a  process  of  dif- 
fusion from  the  subarachnoid  of  the  cord  and  to  a  lesser 
extent  from  the  subarachnoid  of  the  brain.  Some  absorp- 
tion also  takes  place  by  the  lymphatics  draining  into  the 
deep  cervical  glands,  into  the  lymph  vessels  of  the  nose, 
perilymph  spaces  of  the  labyrinth  and  into  the  perineural 
sheets. 

6.  The  cerebrospinal  fluid,  or  rather  the  chorioid  plexus, 
is  not  permeable,  or  very  little  so,  under  normal  conditions. 

7.  The  fluid  exerts  a  mechanical  function  in  that  it  equal- 
izes the  cerebrospinal  pressure.  The  numerous  other  func- 
tions attributed  to  the  fluid  need  further  substantiation. 


46  CEREBROSPINAL  FLUID 

8.  The  origin  of  cerebrospinal  fluid  is  unknown.  Tliere 
is  evidence  pointing  toward  the  theory  that  tlie  cliorioid 
plexus  is  the  seat  of  origin  of  the  fluid.  There  is  also  evi- 
dence pointing  to  the  assumption  that  the  fluid  is  a  direct 
product  of  the  blood.  It  is,  therefore,  plausible  to  assume 
that  the  cliorioid  plexus  plays  the  role  of  separating  the 
various  constituents  of  the  cerebrospinal  fluid  from  the 
blood. 

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1907,  cxxxiii,  567. 
Reicliardt:      Zur   Entstehung   des   Hirndrucks   bei   Hirngeschwiilsten   und   an- 

deren  Hirnkrankheiten  und  iiber  eine  bei  diesen   zu  beobachtende  beson- 

dere  Art  der  Hirnschwellung,  Deutsch.  Ztschr.   f.  Nervenh.,   1905,  xxviii, 

306. 


48  CEREBROSPINAL  FLUID 

Schlaepfer,  V.:     Ueber  den  Bau  und  die  Fuuktion  der  Epithelzellen  des  Plexus 

choroideus    in    Bezielmng    zur    Gvanuladehr    und    mit    besondere    Beriick- 

sichtigung  der  Vitalen  Farbungsmethoden,  Beitr.  z.  path.  Anat.  u.  z.  allg. 

Path.,  Suppl.  vii,  101, 
Schmidt,  Carl:     Charakteristik  der  epideniischen  Cholera,  Leijizig  und  Milan, 

1850,  148. 
Schmorl:       Liquor     cerebrospinalis     und     Ventrikelfliissigkeit,     Verhandl.     d. 

deutsch.  path.  Gesellsch.,  Eilangen,  1910. 
Sicard:      Les   injections    sous-arachnoidiennes   et   le   liquide   cephalo-rachidien 

dans  les  maladies  mentales,  Bull,  de  la  Soc.  nied.  des  hoj).  de  Paris,  June, 

1901. 
Spina:      Untersuchungen  iiber   die  Resorption  des  Liquors  bei  normalen  und 

erhohten  intrakraniellen  Druck.,  Arch.  f.d.  ges.  Physiol.,  1901,  Ixxxiii,  120. 
Spina:      Experimentelle   Beitrage   zur   Kenntniss  der   Hyperamie    des   Hirns, 

1898,  Wien.  med.  Bl.,  247. 
Spina:     tjljer  den  Einfluss  des  hohen  Blutdruckes  auf  Cerebrospinal  Fliissig- 

keit,  Pflugers  Arch.,  1900,  Ixxx,  370. 
Sundwall:       The    Choroid    Plexus     with     Special    Reference     to     Interstitial 

Granular   Cells,   Anat.   Rec,   1917,   xii,   221. 
Weed:  Studies  on  the  Cerebrospinal  Fluid,  Jour.  Med.  Research,  1914,  xxxi,  1. 
Weil    and    Kafka:     tJber    die    Durchgangikeit    der    Meningen,    besonders    bei 

der  progrcssiven  Paralyse,  Wien.  klin.  Wclmschr.,  1911,  xxiv,  3.35. 
Weil   and   Kafka:      Weitere   Untersuchungen   iiber   den   Hamolysingehalt   der 

Zerebrospinalfliissigkeit  bei  akuter  Meningitis  und  progressiver  Paralyse, 

Med.  Klin.,  1911,  vii,  1314. 
Yoshimura:        Das      histochemische      Verhalten      des      mensehlichen      Plexus 

choroideus,  Obersteiner 's  Arbeiten,  1910,  xviii. 
Zaloziecki:     Zur    Frage    der    Permeabilitat    der    Meningen    insbesondere    Ini- 

munstoffen  gegeniiber,  Deutsch.  Ztschr.  f.  Xervonh.,  1913,  xlvi,  195. 
Ziegler:     Beitrag   zur   Anatomie    des    Plexus    chorioideus   Deutsch.    Ztschr.    f. 

Chir.,  1902,  Ixvi,  509. 


CHAPTER  III 

METHODS  OF  OBTAINING  CEREBROSPINAL  FLUID 
FROM  THE  LIVING  BODY 

Before  the  day  of  spinal  puncture  the  removal  of  cere- 
brospinal fluid  from  the  body  was  effected  with  a  great 
deal  of  difficulty.  The  usual  method  of  removing  cerebro- 
spinal fluid  from  dogs  was  by  means  of  a  fistula  between 
the  occiput  and  the  atlas.  From  human  beings  cerebro- 
spinal fluid  was  obtained  through  an  accidental  flow  of  fluid 
from  the  nose  or  ears.  There  are  about  twenty  such  cases 
on  record.  Another  way  of  obtaining  cerebrospinal  fluid 
from  the  living  body,  but  one  used  only  very  rarely,  was 
an  open  operation  either  on  the  head  or  on  the  vertebral 
column. 

At  present  there  are  two  reliable  methods  in  use  for  the 
removal  of  cerebrospinal  fluid  from  man  or  animal.  One 
is  spinal  puncture,  more  properly  called,  lumbar  puncture, 
and  the  other  is  cranial  or  ventricular  puncture.  Both 
procedures  are  comparatively  simple  and  can  be  carried 
out  under  ordinary  conditions  at  the  hospital  or  at  home. 
Lumbar  puncture  is  preferable  for  many  reasons.  We 
shall,  therefore,  discuss  it  more  exhaustively. 

LUMBAR  PUNCTURE 

The  first  lumbar  puncture  by  Quincke  in  1891  was  done 
for  therapeutic  purjjoses.  Since  his  time,  however,  we 
liave  learned  a  great  deal  about  the  value  of  lumbar  punc- 
ture for  diagnostic  as  well  as  for  therapeutic  purposes. 
Therapeutically,  lumbar  puncture  is  done  for  the  relief  of 
increased  intracranial  pressure  as  in  hydrocephalus,  de- 
lirium   tremens,    eclampsia,    encephalitis    and    other    con- 

49 


oO 


CEREBilOSPIXAL  FLUlt) 


vulsive  conditions.  Of  great  value  is  lumbar  puncture  for 
the  purpose  of  injecting  serum  in  cases  of  epidemic  menin- 
gitis, and  for  the  Swift -Ellis  treatment  of  syphilis.  Lum- 
bar puncture  is  also  done  by  some  for  the  relief  of  general 
edema  in  cases  of  nephritis.     Recently,  J.  M.  ]3rady  re- 


Fig.8. — Specimen  illustrating  the  importance  of  spinal  puncture  for  diagnostic  pur- 
poses. S.  C.  entered  the  hospital  with  symptoms  of  pneumonia  and  with  marked 
cyanosis.  At  first  sight  there  seemed  to  be  no  indication  for  a  spinal  puncture,  but  when 
convulsions  set  in,  a  puncture  was  done.  The  fluid  withdrawn  was  very  turbid  and 
showed  pneumococci  in  direct  smear  as  well  as  in  culture.  The  postmortem  showed  a 
well-defined   exudate   of  the  meninges,   the   exudate   containing  many   pneumococci. 


ported  three  cases  of  meningeal  hemorrhage  which  recov- 
ered after  lumbar  puncture.  Cure  by  spinal  puncture  has 
also  been  reported  in  two  eases  of  diabetes  insipidus.  As 
a  general  rule,  therefore,  a  spinal  puncture  should  be  made 


LUMBAR    PUNCTURE 


,51 


in  all  cases  showing  signs  of  increased  intracranial  pres- 
sure. 

Diagnostically,  lumbar  puncture  is  of  great  value  in 
cerebrospinal  lues,  hemorrhage  of  the  brain,  tumors  of  the 
cord,  poliomyelitis,  etc.  It  is  particularly  valuable  in  the 
diagnosis   of  all   forms   of  meningitis   and  poliomyelitis. 


Fig.   9.      Hpiusiic   \i(.\v   uf   i''ig.   S.    (See    Fig.   8   for  description.) 


The  following  cases  are  cited  to  sIioav  how  important  a 
diagnostic  measure  spinal  puncture  may  be : 

S.  C,  entered  the  hospital  with  symptoms  of  pneumonia  and  cyanosis. 
The  lung  findings  were  indefinite.  There  was  very  little  rigidity  of  the 
neck  and  no  other  symptoms  pointing  to  a  meningitis.  At  first  sight  there 
seemed  to  be  no  indication  for  a  spinal  puncture,  but  when  convulsions  set 
in  a  puncture  was  made.  The  fluid  withdrawn  was  turbid  and  showed 
pneumococci  in  smoar  and  culture.  The  postmortem  showed  the  lungs  to 
be    congested,    l)ut    no    pjuMinioiiia.      Tlu'    ccrcbnim,    however,    was    covered 


52  CEREBROSPINAL  FLUID 

with  a  gelatinous,  greenish  gray,  purulent  material  several  millimeters 
thick  and  very  firm;  the  exudate  was  located  on  the  upper  and  lateral  sur- 
faces of  the  brain.  (Figs.  8  and  9.)  The  smears  as  well  as  the  cultures 
showed  gram-positive  cocci. 

Altliougli  in  this  case  not  much  could  be  done  therapeu- 
tically even  if  the  process  had  been  recognized  earlier, 
the  spinal  puncture  was  of  great  value.  It  served  to  es- 
tablish a  positive  diagnosis  in  a  case  in  which  a  meningeal 
exudate  existed  with  few  if  any  of  the  meningeal  symp- 
toms that  usually  accompany  such  a  condition. 

The  case  that  follows  illustrates  even  more  vividly  the 
importance  of  lumbar  puncture: 

S.  W.,  ten  years  old.  Sick  for  five  days.  Complained  of  pain  in  lumbosacral 
region,  and  also  in  the  right  hip,  radiating  to  the  sole  of  the  foot  at  the 
time;  occasionally  there  was  pain  in  the  left  shoulder.  When  first  seen  the 
temperature  was  102°  F.  There  was  tenderness  to  touch  in  the  lumbo- 
sacral and  gluteal  regions,  slight  rigidity  of  the  neck,  slight  Kernig  and 
contralateral  Brudzinski  signs.  The  diagnosis  by  several  physicians  was 
neuritis.  On  lumbar  puncture  a  very  turbid  fluid  was  obtained  under  great 
pressure.  Bacteriologic  examination  showed  meningococci  and  several  hun- 
dred cells  per  cubic  millimeter.  All  gloliulin  tests  were  positive.  The  patient 
was  given  several  doses  of  antimeningocoecus  serum  and  recovery  followed. 

In  this  case  lumbar  puncture  was  a  life-saving  measure. 
In  the  next  case  meningitis  could  hardly  have  been  discov- 
ered without  lumbar  puncture  as  the  general  symptoms 
were  so  indefinite. 

F.  R.,  aged  eight  months.  Sick  one  day  with  fever  and  constipation. 
Had  attack  of  cyanosis  for  a  few  minutes.  General  examination  was  nega- 
tive. Lumbar  puncture  was  done  and  to  the  great  surprise  of  the  physicians, 
the  fluid  was  found  very  turbid  and  fuU  of  meningococci. 

These  cases  are  but  few  of  a  great  number  coming  under 
my  observation  that  illustrate  the  extreme  importance  of 
lumbar  puncture. 

There  are  very  few  counterindications  to  lumbar  punc- 
ture. In  cases  of  tumors  of  the  cerel^rum  and  cerebellum, 
it  is  true  that  puncture  is  not  so  safe  as  under  ordinary 
conditions.  Even  then,  however,  a  lumbar  puncture  may 
be  done  with  little  trei3idation  if  the  pulse  and  reflexes  of 


LUMBAR   PUNCTURE  53 

the  patient  are  watched  and  if  the  amount  and  pressure  of 
the  cerebrospinal  fluid  are  closely  observed. 

Untoward  Effects  of  Lumbar  Puncture 

Cases  of  death  from  spinal  puncture  have  been  reported. 
These,  however,  usually  occurred  in  cases  of  brain  tumor, 
and  death  in  most  instances  was  attributable  to  shock.  Of 
the  many  hundreds  of  punctures  that  have  come  under  my 
observation,  I  saw  onl}^  one  case  of  death  during  puncture. 
Of  other  dangers  attending  spinal  puncture  the  following 
may  be  mentioned:  Piercing  of  the  aorta,  injury  to  the 
nerves,  and  breaking  of  the  needle. 

As  to  piercing  of  the  aorta,  it  must  be  said  that  this 
is  a  very  rare  occurrence,  and  when  it  does  happen  it  is 
due  to  poor  judgment  on  the  part  of  the  operator  as  to  the 
depth  to  which  the  needle  should  be  introduced. 

Injury  to  the  nerves  is  a  complication  that  can  easily  be 
averted  if  the  puncture  is  made  at  a  low  level  in  the  lumbar 
region,  preferably  between  the  third  and  fourth  vertebrae. 

Breaking  of  the  needle  may  result  from  undue  force.  If 
the  needle  is  broken  directly  beneath  the  skin,  it  is  best  to 
incise  the  skin  and  remove  it.  If  it  is  broken  deeper,  how- 
ever, which  is  generally  the  case,  it  is  best  to  leave  it  alone 
for  a  while.  If  no  complications  occur  in  several  days,  it 
is  advisable  to  leave  the  needle  in.  If  severe  pain  or  sup- 
puration occurs,  a  radical  operation  should  be  done  and 
the  needle  removed.  There  are  some  less  severe  complica- 
tions that  may  follow  lumbar  puncture.  The  most  impor- 
tant of  these  are  headache  following  the  puncture,  pain  of 
the  lower  extremities,  and  edema  of  the  skin,  especially  af- 
ter repeated  punctures. 

The  cause  of  headache  after  lumbar  puncture  is  a  mat- 
ter of  speculation.  It  is  generally  attributed  to  the  re- 
moval of  too  great  an  amount  of  fluid  at  one  sitting.  Head- 
ache, however,  sometimes  follows  even  after  the  removal 
of  a  small  amount  of  fluid.    MacRobert  has  recently  sug- 


54  CEREBROSPINAL  FLUID 

gested  that  headache  following  lumbar  puncture  may  be 
due  to  the  nonclosure  of  the  puncture  hole  in  the  arachnoid. 
The  arachnoid  tissue  in  a  case  of  this  kind,  the  author 
says,  is  pulled  through  the  dural  opening  when  the  needle 
is  withdrawn.  This  results  in  prolonged  epidural  leakage 
and  in  the  lack  of  support  of  the  medulla,  a  condition 
which  gives  rise  to  severe  headache.  This  explanation 
sounds  plausible  although  it  requires  corroboration  be- 
fore we  can  accept  it.  AVhen  headache  does  occur  after 
lumbar  puncture  the  best  method  of  treatment  is  to 
put  the  patient  flat  on  his  back  for  several  hours.  Oc- 
casionally it  becomes  necessary  to  resort  to  drugs  for  re- 
lief of  the  condition.  Sodium  and  potassium  bromide  or 
salicylates  may  then  be  emploj^ed.  Rarely  is  it  necessary 
to  use  stronger  remedies  than  these. 

Pain  of  the  extremities  after  lumbar  puncture  is  usually 
due  to  injury  of  one  of  the  filaments  of  the  cauda  equina. 
Rest  in  bed  is  usually  all  that  is  necessary  to  relieve  this 
condition. 

Edema  of  the  skin  in  the  lumbar  region  is  an  infrequent 
complication.  I  have  seen  it  in  but  two  cases  and  then  after 
repeated  punctures.  When  it  does  occur  in  infants,  the 
lumbar  region  should  be  given  a  rest  and  if  necessary  to 
introduce  serum,  it  should  be  injected  into  the  ventricles  of 
the  brain  instead.  When  edema  of  the  skin  occurs  in 
adults,  warm  cloths  should  be  applied  to  the  edematous  re- 
gion and  serum  given  intravenously  until  the  edema  sub- 
sides, after  which  intraspinal  introduction  of  serum  may 
be  resumed. 

In  general,  lumbar  puncture  when  indicated  should  not 
be  feared  because  of  complications. 

Technic  of  Lumbar  Puncture 

To  do  a  spinal  puncture  properly  one  must  take  into  con- 
sideration a  numljer  of  important  factors. 

1.  The  anatomic  relations  of  the  cord  and  its  membranes 
at  the  lumbar  region. 


LUMBAR   PUNCTURE 


55 


Tlie  cord,  in  tlie  adult,  ends  at  the  first  lumbar  vertebra, 
and  in  the  child,  at  the  second  vertebra,  seldom  at  the  third. 


Fig.   10. — Section  of  caiitia  equina  of  a  (Ior.     A,  Membranes  intact;  B,  Dura  and  araciinoid 

cut   open. 


56 


CEREBROSPINAL  FLUID 


The  cord  lias  its  ending  in  the  conus  medullaris,  the  apex 
of  which  is  continuous  with  the  filum  terminalis.  Througli- 
out  its  entire  length  the  cord  is  surrounded  by  three  mem- 
branes, the  dura,  the  arachnoid  and  the  pia.  The  accom- 
panying drawing  (Fig.  10)  shoM^s  the  membranes  surround- 
ing the  cord  and  the  cauda  equina  in  a  dog.  The  same  re- 
lations also  hold  good  in  man. 

2.  The  structures  encountered  between  the  skin  and  the 
cord,  wdiicli  are  as  follows  from  wdthout  inward: 

(a)  Skin. 

(b)  Subcutaneous  fascia. 

(c)  Fat. 

(d)  Deep  fascia. 

(e)  Multifidus  muscle, 

(f)  Vertebral  arches. 

(g)  Ligamentum  flavum. 
(h)  Dura. 

(i)  Arachnoid. 


Fig.   11. — Ple.xus  of  veins,  the  puncture  of  which  is  responsible  for  blood  obtained  during 
spinal  puncture.      (Gray's  Anatomy.) 


3.  The  plexus  of  veins  on  the  posterior  wall  of  the  body 
of  the  vertebra  (Fig.  11).  If  these  are  struck  by  the 
spinal  puncture  needle  the  resultant  fluid  is  bloody. 

Another  matter  for  consideration  in  lumbar  puncture 
is  the  position  of  the  patient,  particularly  if  the  patient 
is  a  child.     While  in  an  adult  the  physician  may  do  the 


LUMBAR    PUNCTURE  57 

puncture  with  the  patient  in  either  the  sitting  or  reclin- 
ing position,  in  a  child  he  should  not  attempt  the  punc- 
ture Avitli  the  patient  in  any  but  a  reclining  posture.  In 
all  cases  of  meningitis  the  patient  should  be  in  the  lying 
posture  when  the  puncture  is  performed.  I  always  made 
it  a  practice  to  puncture  with  the  patient  in  a  recumbent 
position.  The  patient  may  be  placed  on  either  right  or 
left  side,  the  right  being  the  preferable  one  for  the  pa- 
tient, who  should  be  arched  so  as  to  widen  the  interverte- 
bral space. 

The  skin  should  be  prepared  very  carefully  for  the  punc- 
ture. Soap  and  water,  alcohol  and  iodine  should  be  used 
for  cleansing  purposes.  Rubber  gloves  should  be  worn  and 
all  other  aseptic  precautions  must  be  taken  to  minimize  the 
danger  of  infection  of  the  meninges.  As  a  rule  neither  a 
general  nor  a  local  anesthetic  is  called  for  in  doing  spinal 
puncture.  It  may  be  necessary  to  resort  to  an  anesthetic 
in  maniacal  cases,  although  I  have  not  encountered  a  single 
case  in  which  I  could  not  get  along  without  it.  Sophian 
suggests  that  the  patient  be  given  water  to  drink  during 
lumbar  puncture.  He  found  that  this  procedure  made  an 
anesthetic  unnecessary.  As  a  rule,  however,  even  this  is 
not  necessary. 

The  Spinal  Puncture  Needle 

Regular  spinal  puncture  needles  are  now  made  measur- 
ing from  7  to  9  cm.  in  length  and  0.6  to  1.2  mm.  in  thick- 
ness with  a  stylet  to  fit  the  needle  (Fig.  12).  Some  needles 
are  made  with  valves  for  the  measurement  of  the  pressure 
of  the  fluid.  Most  needles  on  the  market  are  made  of  steel, 
although  there  are  some  nickel-plated  ones  and  some  made 
of  platinum  iridium.  If  meningitis  is  not  suspected  a  nee- 
dle with  a  small  lumen  will  do,  but  if  there  is  the  slightest 
suspicion  of  meningitis  a  needle  with  a  large  lumen  should 
be  used.  In  children  it  is  always  best  to  use  a  needle  with 
a  large  lumen,  so  that  in  case  the  fluid  is  thick  it  will  not 


58 


CEREBROSPINAL  FLUID 


clog  up  the  needle.  Tlie  needle  sliould  be  boiled  and  cooled 
before  using.  It  should  also  be  examined  very  closely  for 
rust. 

Quincke's  advice  that  the  needle  be  introduced  directly 
in  the  midline  in  children  and  5  to  10  mm.  to  the  side  in 


Fig.  12. — \'arious  types  of  lumbar  i)uncture  needles. 


adults,  holds  good  to  this  day.  If  the  needle  is  inserted  in 
the  third  or  fourth  interspace,  cerebrospinal  fluid  may  be 
withdrawn  without  injury  to  the  nerves.  A  good  landmark 
for  the  guidance  of  the  needle  may  be  made  by  drawing 


LUMBAR    PUNCTURE  59 

a  horizontal  line  througli  the  vertebral  column  across  the 
crests  of  the  ilium.  I  usually  draw  this  line  with  tincture 
of  iodine  on  a  swab.  This  strikes  the  interspace  between 
the  third  and  fourth  vertebra. 

It  is  often  quite  difficult  to  feel  the  intervertebral  space 
in  fat  people  and  in  very  young  children.  Because  of  this 
difficulty  extreme  care  is  necessary  in  cases  of  this  kind. 

*'How  much  of  the  needle  should  be  introduced  into  the 
canal?"  is  one  of  the  first  questions  that  greets  the  inex- 
perienced operator.  In  consulting  literature  on  the  sub- 
ject I  found  very  little  information  about  the  length  of  the 
needle,  the  only  tabulated  data  available  being  by  Quincke, 
who,  however,  cites  only  a  few  cases. 

Table  I 
Measurements  by  Quincke 


AGE 

DEPTH 

1% 

years 

2. 

cm. 

7 

t  ( 

2.5 

<  < 

3. 

<  c 

3. 

1 1 

2.7 

(3.5)cm. 

3.2 

2 

(< 

2.5 

IVi 

1 1 

2, 

25 

e  t 

1.5 
6. 

6.5 

(4.7)" 

39 

1 1 

5  plus      " 

22 

1  e 

5.2 

<  ( 

I  measured  the  length  of  the  needle  in  a  series  of  several 
hundred  cases,  adopting  the  following  procedure:  When 
ready  to  remove  the  needle  from  the  spinal  canal  after  ob- 
taining a  good  flow  of  fluid,  I  grasped  the  needle  close  to 
the  patient's  skin  between  the  thumb  and  index  finger, 
pulled  it  out,  and  measured  it  from  the  point  held  by  the 
fingers  to  the  tip. 


60 


CEREBROSPINAL  FLUID 
Table  II 

MEASrREMEXTS  OF  NeEDLE  IN   CHILDREN 


NAME 


AGE 


LENGTH  OP  NEEDLE  IN  CM. 


R.  R. 

4  mon 

E.  D. 

5   " 

A.  J. 

6   " 

A.  S. 

6   " 

I.  G. 

6   " 

E.  H. 

7   " 

E.  G. 

8   " 

E.  G. 

9   " 

A.  C. 

12   " 

S.  K. 

12   " 

A.  N. 

14   " 

A.  N. 

14   " 

J.  S. 

21   " 

M.  M. 

22   " 

T.  K. 

2  yeai 

T.  K. 

2   " 

R.  P. 

2   " 

F.  W. 

3   " 

J.  M. 

3   " 

M.  H. 

3   " 

M.K. 

3   " 

McM. 

4   " 

H. 

4   " 

P.  0. 

4   " 

W.  J. 

5   " 

R.L. 

6   " 

A.  G. 

7   " 

G.  M. 

8   " 

S.  L. 

8   " 

S.  B. 

9   " 

S.  B. 

9   " 

S.  B. 

9   " 

E.  D. 

9   " 

R.  A. 

10   " 

L.  G. 

12   " 

L.  G. 

12   " 

ths 


7  mos. 


2.0 
2.2 
2.0 
2.3 
2.5 
2.5 
2.4 
2.2 
2.2 
2.0 
2.8 
2.5 
3.5 
3.0 
2.7 
2.1 
2.4 
4.0 
2.0 
2.8 
2.9 
3.2 
2.9 
2.8 
3.2 
3.0 
4.0 
3.5 
3.5 
3.7 
3.4 
4.0 
3.8 
3.6 
3.2 
3.6 


Table  II  gives  the  measurements  of  the  needle  made  in 
children  from  four  months  to  twelve  years  of  age  and  Table 
III  gives  the  measurements  in  adults  of  various  ages.  I  in- 
clude here  but  a  few  of  the  several  hundred  of  measure- 
ments made.  In  cases  in  which  the  results  were  similar  I 
tabulated  but  one  measurement;  in  cases  of  the  same  age 


LUMBAR  PUNCTURE  61 

Taule  III 
Measurements  of  Needle  in  Adults 

ame  age  length   of   needle  in  cm. 

'~  5A 
4.8 
5.0 
5.3 
5.8 
4.9 
5.5 
5.6 
4.5 
5.4 
5.2 
5.8 
5.6 
5.5 

10.0  (very  fat) 
5.1 
4.1 
5.1 
5.1 
5.2 
4.5 
4.6 
5.7 
4.8 
5.5 
4.1 
5.3 
5.5 
5.9 
5.0 

7.0  (very  fat) 
6.0 
6.4 
4.9 
5.0 
6.4 
5.0 
6.3 
4.5 
4.9 
5.8 
5.5 
5.5 
4.9 
4.9 

^-^  (Cont'd  p.   62) 


S.  G. 

16 

years 

T.  E. 

20 

<  ( 

C. 

25 

<  ( 

P. 

26 

( ( 

K. 

27 

1 1 

Mrs.  D. 

29 

1 1 

L. 

29 

1 1 

A.  C. 

30 

n 

E. 

30 

1 1 

D. 

30 

1 1 

H. 

30 

1 1 

E. 

30 

( I 

A.  C. 

30 

<  < 

T. 

31 

<  < 

J.  T. 

31 

<  ( 

Mrs.  D. 

32 

(  ( 

AC. 

33 

1 1 

L.  N. 

33 

<  I 

M. 

34 

t  < 

P. 

34 

<  ( 

S.  G. 

34 

a 

S. 

34 

ti 

M. 

35 

1 1 

M. 

35 

(  ( 

E. 

35 

<  1 

H. 

36 

{ ( 

M.  W. 

37 

I  ( 

I.G. 

37 

1 1 

D. 

37 

1 1 

S.  S. 

38 

1 1 

J.  J. 

39 

1  t 

s. 

40 

( I 

p. 

40 

1 1 

M. 

40 

11 

W. 

40 

I  c 

E. 

40 

1  i 

E. 

42 

t  i 

W. 

43 

1 1 

K. 

43 

I  ( 

M.  B. 

44 

1 1 

J.  A. 

44 

1  < 

W. 

44 

( < 

S. 

45 

1 1 

F. 

46 

(I 

Mrs.  B. 

48 

( t 

M. 

48 

t  ( 

62  CEREBROSPINAL  FLUID 

Table  III— Cont 'd 
Measurements  op  Xeedle  ix  Adults 


NAME 

age 

LENGTH  OF  XEEDLE  IX  CM. 

L. 

48 

years 

5.5 

S. 

52 

5.2 

R. 

53 

5.1 

B. 

53 

10.0  (very  fat) 

B. 

53 

6.0 

H. 

54 

5.2 

W. 

55 

5.3 

S. 

55 

6.7 

D. 

57 

5.4 

A. 

57 

5.6 

M.  R. 

60 

4.1 

F. 

60 

5.9 

K. 

60 

6.0 

B. 

60 

5.9 

S. 

61 

5.9 

w. 

65 

8.0 

where  the  measurements  were  different  several  measure- 
ments are  tabulated.  In  some  cases  the  results  of  several 
measurements  are  given  for  the  same  patient  to  show 
the  length  of  the  needle  at  different  punctures.  As  is  seen 
from  the  tables  the  needle  requires  a  length  varying  from 
2.0  to  4.0  cm.  in  children  up  to  twelve,  and  a  length  varying 
from  4.1  to  10  cm.  in  people  over  sixteen  years  of  age.  The 
variations  in  the  adult  may  be  attributed  to  several  fac- 
tors. Physique  is  one;  the  direction  taken  by  the  operator 
in  inserting  the  needle  is  another,  an  oblique  insertion  nat- 
urally requiring  a  greater  length  of  needle  than  a  straight 
insertion.  The  location  of  the  interspace  is  another  fac- 
tor, the  higher  the  point  of  insertion,  the  greater  being  the 
length  of  the  needle  required.  Some  clinicians  use  as  the 
place  of  introduction  the  space  between  the  second  and 
third  lumbar  vertebrae,  others  the  space  between  the 
first  and  second.  It  is  also  interesting  to  note  that  the 
length  of  needle  inserted  varies  at  different  punctures  in 
the  same  patient.  This  is  due  to  the  fact  that  the  canal  is 
quite  wide  and  that  fluid  may  be  removed  whether  the  nee- 


LUMBAK    PUNCTURE  63 

die  is  near  the  anterior  or  near  the  posterior  surface  of  the 
canal. 

When  the  needle  passes  the  dura,  a  snap  is  felt.  The 
stylet  should  then  be  removed  and  the  fluid  allowed  to 
run  into  the  pressure  apparatus  or  into  tubes. 

Reasons  for  Failure  to  Obtain  Fluid 

There  are  times  when  no  fluid  can  be  obtained  in  spite  of 
all  efforts.  Among  the  factors  responsible  for  the  failure 
to  obtain  fluid,  the  most  important  are  the  following: 

1.  The  needle  may  not  have  been  inserted  far  enough  into 
tl^e  canal. 

2.  The  needle  may  have  been  introduced  too  far  into  the 
canal.  In  such  cases  the  material  exuding  from  the  inter- 
vertebral disc  may  clog  up  the  needle. 

3.  The  presence  of  blood  in  the  fluid. 

The  presence  of  blood  is  by  far  the  most  common  cause 
of  failure  in  lumbar  puncture.  It  may  be  due  to  hemor- 
rhage of  the  brain  or  to  piercing  some  vein  of  the  plexus 
in  the  spinal  canal.  If  the  presence  of  blood  in  the  fluid  is 
due  to  the  striking  of  the  plexus  of  veins,  the  exuding  fluid 
has  the  color  of  fresh,  venous  blood.  If  it  is  due  to  a  hemor- 
rhage, the  blood  in  the  fluid  is  a  dark  red,  and  if  the  hemor- 
rhage is  one  of  long  standing,  clotted  particles  of  blood 
may  be  seen  clinging  to  the  needle  or  coming  out  of  the 
lumen. 

If  no  fluid  is  obtained  the  stylet  should  be  reintroduced 
into  the  needle  to  clear  it  of  any  particles  that  may  be 
clogging  the  lumen,  and  it  should  then  be  withdrawn  again. 
If  there  is  still  no  sign  of  fluid  the  needle  should  be  moved 
a  little  deeper  or  withdrawn  slightly.  If  flmd  is  still  not 
forthcoming,  the  needle  should  be  removed  and  reintro- 
duced one  space  higher.  If  after  this  procedure  there  is 
still  no  fluid  an  ethylchloride  spray  applied  to  the  thigh 
may  accelerate  the  flow.  If  after  repeated  trials  no  fluid 
escapes,  one  may  ascertain  whether  the  spinal  canal  has 


64  CEREBROSPINAL  FLUID 

been  reached  by  the  following-  method:  The  first  needle 
is  left  in  its  original  position,  and  a  second  needle  is  intro- 
duced one  space  higher.  A  solution  of  sterile  salt  is  in- 
jected into  the  higher  needle.  If  the  first  needle  is  in  the 
canal,  the  salt  solution  will  flow  out  of  it.  When  this  hap- 
pens it  indicates  that  in  all  probability  no  fluid  can  be  ob- 
tained. As  a  rule  one  should  be  careful  about  pronounc- 
ing a  puncture  dry.  A  failure  to  obtain  fluid  may  nearly 
always  be  attributed  to  some  fault  in  the  technic. 

If  the  case  shows  symptoms  of  meningitis  in  spite  of  the 
fact  that  no  fluid  can  be  obtained  by  the  spinal  route,  it 
may  concern  a  basilar  meningitis  in  which  it  often  happens 
that  the  connection  between  the  brain  and  cord  becomes 
clogged.  In  such  a  case  ventricular  puncture  should  be 
done.  The  technic  of  ventricular  puncture  will  be  de- 
scribed later. 

Pressure 

The  measurement  of  the  pressure  of  the  cerebrospinal 
fluid  is  very  significant  from  the  standpoint  of  diagnosis 
as  it  furnishes  an  almost  immediate  clew  as  to  the  existence 
of  a  pathologic  condition.  It  should,  therefore,  be  used  in 
connection  with  lumbar  puncture  whenever  possible. 

Various  forms  of  apparatus  have  been  described  for  the 
determination  of  the  cerebrospinal  fluid  pressure.  Quincke 
used  an  ordinary  glass  tube  with  a  one-millimeter  bore 
bent  at  the  top,  and  an  ordinary  tape  to  measure  the  pres- 
sure :  an  arrangement  like  the  one  used  by  Quincke  may  be 
made  at  any  laboratory  by  taking  heavy  glass  tubing  of 
one-millimeter  bore,  bending  it  at  right  angles  below,  and 
connecting  it  with  hard  rubber  of  one-millimeter  bore  to 
a  tip  fitting  into  an  ordinary  spinal  puncture  needle.  The 
point  to  which  the  fluid  reaches  can  be  marked  off  and  the 
height  can  then  be  measured  on  a  slide  or  with  a  tape  meas- 
ure (Fig.  13).  I  use<l  this  arrangement  for  some  time, 
but  although  it  is  of  value,  it  is  not  accurate  enough.    The 


LUMBAR   PUNCTURE  65 

disadvantage  of  the  Quincke  apparatus  lies  in  the  fact 
tliat  it  takes  too  much  time  to  attach  the  glass  tubing  to  the 
needle.     It  frequently  happens  that  the  pressure  of  the 


Fig.    13. — Modified  Ouineku  apjiaratus   for  nitasiiiing  tlie  cerebrospinal  fluid   pressure. 

fluid  is  so  great  that  as  soon  as  the  stylet  is  removed  from 
tlie  needle,  the  fluid  bursts  out,  and  several  cubic  centime- 
ters of  fluid  are  lost  before  the  tip  of  the  pressure  ap- 
paratus can  be  connected  to  the  needle.     In  this  way  the 


66  CEREBROSPIXAL  FLUID 

real  pressure  value  can  not  be  ascertained,  as  it  is  known 
that  once  a  few  cubic  centimeters  of  fluid  are  removed,  the 
original  cerebrospinal  pressure  is  not  maintained. 

Several  other  types  of  apparatus  have  been  described. 
One  is  by  Kroenig,  utilized  principally  for  the  purpose  of 
withdraw^ing  fluid  from  suspected  cases  of  brain  tumor. 
The  caliber  of  the  measuring  tube  is  so  small,  that  it  only 
takes  a  few  drops  to  fill  it,  and  when  the  column  of  fluid 
shows  no  oscillation,  no  more  fluid  should  be  withdrawn. 

Some  authors  have  used  a  mercury  manometer.  In  nor- 
mal cases,  however,  I  have  found  the  pressure  to  be  too 
small  to  be  measured  in  millimeters  of  mercury,  as  each 
millimeter  of  mercury  corresponds  to  13  mm.  of  water. 
Thus,  for  instance,  when  the  pressure  of  the  fluid  is  65  mm. 
of  water,  the  mercury  manometer  registers  only  four  and 
one-half  or  five,  making  too  great  an  error  in  the  reading. 
As  for  the  objections  raised  against  the  ordinary  one  mm. 
bore  that  it  is  too  small  and  that  it  exerts  capillary  trac- 
tion, it  must  be  said  that  after  all  since  the  value  of  pres- 
sure reading  lies  in  the  comparison  between  the  normal 
and  pathologic  capillary  traction  is  not  a  great  factor. 

In  my  experiments  on  pressure  I  have  been  using  an  ap- 
paratus which  allows  no  loss  of  fluid  and  which  has  the 
added  advantage  of  being  simple. 

The  apparatus  (Fig.  14)  consists  of  a  specially  devised 
needle  and  a  glass  manometer. 

The  needle  is  the  ordinary,  medium-sized,  spinal  punc- 
ture needle  with  a  short  piece  of  glass  mounting.  The 
glass  tubing  enables  one  to  see  whether  the  spinal  canal 
has  been  reached  with  the  first  puncture.  In  the  ordinary 
spinal  puncture  needle,  one  must  withdraw  the  stylet  en- 
tirely before  one  can  see  wdiether  or  not  the  spinal  canal 
has  been  reached,  thus  running  the  risk  of  losing  some  fluid 
before  the  pressure  can  be  measured.  AVith  the  glass  tub- 
ing on,  one  need  onh*  withdraw  the  stylet  beyond  the  glass 
tubing,  and  if  the  spinal  canal  has  been  reached,  the  fluid 


LUMBAR   PUNCTURE 


67 


witlidrawn  will  be  seen  immediately  through  the  glass. 
On  the  other  hand,  if  no  fluid  makes  its  appearance,  the 
stylet  can  be  inserted  again  and  another  attempt  made. 


''■K-  l-t- — Author's  spinal  puucture  needle  and  manometer;  A,  glass  tubing  in  the 
needle;  B,  stoi)cock;  C,  upper  projection  of  the  needle  into  which  the  manomteter  is  in- 
troduced;  U,  glass  manometer. 

The  fear  of  breaking  the  glass  on  boiling  the  needle 
and  sterilizing  it  is  not  a  very  strong  objection.  I  have 
boiled  needles,  repeatedly,  without  ever  breaking  the  glass. 


68  CEREBROSPINAL  FLUID 

The  glass  tubing  may  be  slipped  into  the  needle  instead  of 
being  mounted,  making  possible  the  use  of  any  form  af 
spinal  puncture  needle.  At  the  distal  end  of  the  glass  tub- 
ing the  needle  has  a  three-way  stopcock,  the  distal  end  of 
which  is  about  three-fourths  of  an  inch  long.  This  length 
is  required  in  order  to  allow  space  from  the  stopcock  to 
the  end  of  the  needle  so  as  not  to  lose  any  of  the  fluid  as  is 
the  case  when  the  valve  of  the  stopcock  is  near  the  end  of 
the  needle.  The  stylet  of  the  needle  is  long  enough  to 
reach  from  the  distal  to  the  proximal  end  of  the  needle. 

The  manometer  consists  of  a  long  glass  tube  of  one  mm. 
bore  which  is  inserted  into  the  projecting  end  of  the  nee- 
dle. The  glass  tubing  is  800  mm.  long  as  this  was  the 
highest  pressure  attained  in  any  case,  and  for  convenience 
sake,  it  is  divided  into  two  portions  with  a  metal  cap  at 
the  top  of  the  first  portion  so  that  the  other  one  can  be 
screwed  on.  This  makes  it  convenient  to  carry  the  manom- 
eter in  anj^  small  instrument  case.  Thick  glass  tubing  is 
used  for  it  so  that  it  does  not  break  easily  in  handling.  A 
metal  tape  is  attached  to  the  glass  to  measure  the  pressure. 
This,  however,  can  be  done  away  with  and  a  ruler  used  in- 
stead, or  have  the  glass  tubing  graduated. 

The  needle  (with  the  piece  of  glass  tubing  at  the  end,  the 
stopcock  and  its  prolongation  with  the  stylet  inside)  is  in- 
troduced into  the  spinal  canal.  After  a  snap  has  been  felt, 
so  that  one  is  reasonably  certain  the  subdural  canal  is 
reached,  the  stylet  should  be  removed  to  a  point  beyond  the 
glass  attachment.  If  fluid  is  seen  in  the  glass  tubing,  the 
stopcock  is  turned  at  right  angles  so  that  the  handle  points 
upwards.  The  long  glass  tube  is  then  attached  and  the 
stopcock  turned  so  that  the  handle  points  opposite  the 
manometer.  The  fluid  will  then  rush  into  the  tube.  When 
the  fluid  has  mounted  to  the  highest  point,  the  pres- 
sure is  read  off  in  millimeters  of  water.  If  no  fluid  is  seen 
coming  out  when  the  stylet  is  removed  beyond  the  glass 
tubing,  the  stylet  should  be  reintroduced  until  the  operator 


LUMBAR    PUIS^CTURE  69 

feels  it  is  in  the  canal.  It  should  then  be  removed  beyond 
the  glass  and  the  measurement  taken.  The  handle  is  now 
turned  parallel  to  the  needle  and  the  fluid  is  collected  in 
test  tubes.  The  whole  needle,  including  the  glass  attach- 
ment, stopcock,  and  prolongation  is  not  any  heavier  than 
an  ordinary  medium-sized  spinal  puncture  needle. 

If  no  ])ressui('  ajjpai'atus  is  available,  counting  the  drops 
and  noting  the  force  with  which  the  fluid  comes  out  from 
the  needle  will  give  a  clew  to  the  pressure,  anything  above 
ten  drops  per  minute  indicating  an  abnormal  condition. 
I  should  like  to  remind  the  reader  once  more  that  the  pres- 
sure must  be  taken  at  the  very  beginning,  as  after  several 
cubic  centimeters  of  fluid  have  been  removed,  the  pressure 
lets  up  and  determination  then  becomes  practically  value- 
less. 

Collection  of  the  Fluid 

Some  persons  collect  cerebrospinal  fluid  in  graduated 
medicine  glasses,  so  as  to  be  able  to  measure  the  exact 
amount.  This  method  of  collection,  however,  is  not  advis- 
able as  it  is  hard  to  keep  the  fluid  sterile  in  a  wide  glass, 
and  it  is  also  hard  to  observe  the  characteristic  pellicle.  I 
therefore,  advise  the  collection  of  cerebrospinal  fluid  in 
test  tubes. 

The  test  tubes  in  which  the  fluid  is  to  be  collected  should 
be  sterile  and  chemically  clean.  It  is  best  to  use  tubes  of 
uniform  size.  The  glass  of  the  tube  should  not  be  too 
thick  and  its  opening  should  be  stoppered  Avith  a  cotton 
plug,  unless  special  tests  requiring  a  slow  escape  of  CO2 
are  to  be  made.  For  the  sake  of  uniformity  and  because 
of  the  difference  in  the  cell  content  of  various  portions  of 
the  cerebrospinal  fluid,  the  following  method  has  been 
found  useful  in  cases  where  a  quantity  greater  than  5  c.c. 
of  fluid  is  withdrawn: 

Several  drops  of  the  fluid  are  allowed  to  run  out  of  the 
needle  to  make  sure  that  the  fluid  is  free  from  blood.    The 


70  CEREBROSPIXAL  FLUID 

entire  amount  is  then  collected  into  three  tubes  of  uniform 
size.  In  the  first  test  tube  is  run  the  first  2  c.c.  of  fluid. 
This  amount  is  used  for  several  different  examinations: 
(1)  cytologic  examination;  (2)  direct  smear  for  micro- 
organisms if  the  fluid  is  turbid;  (3)  cultures;  (4)  1  c.c.  for 
the  permanganate  test.  The  contents  of  the  first  tube 
should  be  examined  immediately.  If  it  is  not  examined 
immediately,  the  test  tube  with  its  contents  should  be 
placed  in  the  incubator. 

In  the  second  test  tube,  3  to  5  c.c.  of  fluid  is  collected. 
If  the  pressure  is  not  increased  the  contents  of  this  test 
tube  should  be  used  for  the  globulin  tests,  Wassermann 
and  Lange.  If  the  pressure  is  increased  the  test  tube  should 
be  put  into  a  tube  rack  for  the  formation  of  a  pellicle.  Care 
should  be  taken  that  the  mixture  is  not  disturbed. 

If  there  is  a  large  amount  of  fluid  present  a  third  and 
fourth  tube  should  be  taken.  Into  the  third  tube  should 
be  run  from  5  to  8  c.c.  of  fluid.  This  fluid  should  be  used 
for  (1)  the  second  portion  of  the  permanganate  test;  (2) 
the  Koss-Jones,  Noguchi  and  Nonne,  and  the  sulphosali- 
cylic-mercuric  chloride  tests;  (3)  Lange  test;  (4)  Wasser- 
mann test;  (5)  sugar  content;  (6)  centrifugation,  for  the 
examination  of  organisms. 

Into  the  fourth  tube  should  be  run  all  the  rest  of  the 
fluid  desired  for  collection. 

In  normal  cases  where  the  pressure  is  not  increased  only 
5  to  10  c.c.  of  fluid  should  be  withdrawn.  In  all  cases  of 
increased  pressure  a  greater  quantity  of  fluid  should  be 
removed.  In  delirium  tremens,  10  c.c.  usually  suffices  to 
quiet  the  patient.  In  meningitis,  15  to  40  c.c.  may  be  with- 
drawn on  account  of  the  greatly  increased  amount  of  fluid 
in  the  canal.  Even  in  the  severe  cases  of  meningitis,  how- 
ever, it  is  not  advisable  to  remove  more  than  40  c.c.  at  one 
sitting  on  account  of  the  danger  of  inducing  shock.  The 
quality  of  the  pulse  is  a  good  guide  as  to  the  amount  of 
fluid  to  remove. 


LUAIBAR   PUNCTURE  71 

After  the  needle  is  witlidrawn  collodion  should  be  put 
on  the  wound  and  the  skin  should  be  washed  off  if  iodine 
has  been  applied  before  the  puncture.  The  patient  should 
be  put  to  bed  immediately  after  the  puncture  to  prevent 
headache  or  dizziness. 

CRANIAL  PUNCTURE 

When  no  cerebrospinal  fluid  can  be  drawn  by  way  of 
lumbar  puncture  and  it  is  found  urgent  to  obtain  some  for 
diagnostic  or  therapeutic  purposes  as  is  the  case  when 
meningitis  is  suspected  or  present,  cerebrospinal  fluid  may 
still  be  obtained  by  cranial  routes,  either  from  the  sub- 
arachnoid of  the  brain  or  from  the  ventricles.  The  amount 
of  fluid  obtainable  from  the  subarachnoid  space  at  best  is 
small  and  the  procedure  is  difficult.  It  is  therefore  always 
advisable  to  remove  the  fluid  from  the  ventricles.  The 
technic  employed  for  a  ventricular  puncture  in  infants 
when  the  anterior  fontanelle  is  not  yet  closed,  is  as  follows: 

The  patient  is  placed  on  the  back  with  the  head  close  to 
the  edge  of  the  table.  The  head  around  the  region  of  the 
anterior  fontanelle  is  shaved,  and  washed  mth  alcohol 
and  ether.  Iodine  is  applied  to  the  surface.  The  needle 
to  be  used  should  be  sterilized  and  all  other  necessary 
aseptic  precautions  should  be  taken.  A  short  spinal  punc- 
ture needle  or  an  ordinary  Luer  needle  should  be  used.  The 
stylet  should  be  left  in  the  needle  the  same  as  in  lumbar 
puncture,  for  if  the  stylet  is  removed  brain  tissue  may  clog 
the  needle  and  prevent  the  flow  of  fluid.  The  needle  should 
be  introduced  from  V/2  to  1%  inches  deep  and  the  stylet  re- 
moved. The  needle  should  be  inserted  into  the  anterior  an- 
gle of  the  anterior  fontanelle,  in  a  somewhat  oblique  direc- 
tion, a  little  to  one  side  of  the  median  line  (Figs.  15  and  16) 
as  piercing  of  the  longitudinal  sinus  will  give  blood  in  the 
fluid.  After  the  desired  amount  of  fluid  is  obtained,  the 
needle  is  removed  and  collodion  applied  to  the  punctured 
surface. 


72 


CEREBROSPINAL  FLUID 


In  adults,  cranial  puncture  is  most  generally  made  for 
therapeutic  purposes,  especially  for  the  relief  of  intra- 
cranial pressure.  It  necessitates  the  use  of  a  bore  or  a  tre- 
phine to  get  through  the  skull.  The  method  used  is  tliat  of 
Kocher,  consisting  of  a  trephine  opening  2.5  cm.  from  the 


Kig.    15. — Photograph  showing  ventricular  puncture   in   infant.      Dark   circular   spot   shows 
needle   in  position.      (Front   view.) 


median  line  and  3  cm.  in  front  of  the  coronal  or  frontopa- 
rietal suture.  The  needle  is  then  passed  inward  and  slightly 
backward  for  a  distance  of  4  or  5  cm.  when  the  lateral  ven- 
tricle is  reached.  The  operation,  in  general,  is  a  rather 
complicated    one    and    calls    for    precision    and    careful 


LUMBAR    PUNCTURE 


73 


surgical  technic.  It  should  therefore  be  used  only  when 
absolutely  necessary.  The  rule  should  be  to  do  a  lumbar 
puncture  whenever  possible,  but  when  fluid  can  neither  be 
obtained  nor  introduced  by  way  of  lumbar  puncture,  then 
ventricular  puncture  should  be  made,  especially  in  the  case 
of  infants. 


Fig.    16. — I'hoiograph    showing   ventricular   puncture    in    infant.    (Side    view.) 


Bibliogfraphy 

Brady:     Lumbar  Puncture  in  Meningeal  Hemorrhage  of  the  New  Born,  Jour. 

Am.  Med.  Assn.,  1918,  Ixxxi,  347. 
Curschman :       uljer    die    tlierapeutische    Bedeutung    der    Lumbalpunktion,    Die 

Therapie  der  Gcgenwart,   1912,  lii,  242. 
Funkhauser:      Erfalirungen    ii1)er   Lumbalpunktion    Ijei    Geisteskranken,    Kor- 

respondenzl)l.  f.  Schweiz.  Arzte,  1907,  xxvii,  33. 
Graham:     Spinal  Puncture  in  Dia])etes  Insipidus,  Jour.  Am.  Med.  Assn.,  1917, 

IxLx,  1498. 


74  CEREBROSPIiSrAL  FLUID 

Gumprecht :     Gefahren  bei  der  Lumbalpunkl  ion  plotzliche  Todcsf alle  darnach., 

Deutscli.  med.  Wchuschr.,  1900,  xxvi,  386. 
Juvara:     Topographic  de  la  region  lombaire  en  vue  de  la  ponction  dii  canal 

rachidien,  Semaine  med.,  1907,  No.  9. 
Kroenig:      tjber  Lumbalpunktion   bei  Eclampsia,   Zentralbl.    f.   Gynak.,   1904, 

xxxix,  1153. 
Kroenig   und    Gauss:      Anatomische    und    pliysiologisclie    Beobachtimg    ersten 

tausend    Riickenniarksaiiasthesien    Miinchen.    med.    Wchnschr.,    1907,    liv, 

1969. 
Levinsnn :      Measurements    of    the   Spinal    Puncture    Needle,   Jour.    Lab.    and 

Clin.  Med.,  1917,  iii,  127. 
Levinson :      An   Impro.ved   Spinal   Puncture   Needle   and   Pressure  Apparatus, 

Jour.  Am.  :\Ied.  Assn.,  1919,  Ixxii,  .344. 
MacRobert:     The  Cause  of  Lumbar  Puncture  Headache,  Jour.  Am.  Med.  Assn., 

1918,  Ixx,  1350. 
Neisser  and  Pollak:     Die  Hirnpunktion  und  Punktion  des  Gehiras  und  seiner 

Haute  dureh  den  intakten  Scliadel,  Grenzgebiete  der  Mediz.  und  Chirurg., 

1904,  xiii,  807. 
Ossipow:     tJber  die  pathologische  Veranderungeu  welehe  in  dem  Central  Ner- 

vensygtem  von   Tieren   durch  die   Luml)alpunktion  hervorgerufcn   werden, 

Deutsch.  Ztschr.  f.   Nervenh.,   1901,  xix,  105. 
Pfeiffer:      tJber  explorative   Hirnpunktion   zur   Diagnose   von   Hirn,   Arch.   f. 

Psych,  u.  Nervenh.,  xlii,  No.  2. 
Quincke:      IJber   Hydrocephalus,   Verhandl.    d.    Cong.    f.    inn.    Med.,    1891,   x, 

321. 
Quincke:      Die   Technik  der  Liunbalpunktion,  1902. 
Quincke:      Ueber  Lumbalpunktion,  Deutsch.  Klin.,   1906,  vi. 
Schemensky:      Lumbalpunktion   bei   Typhus,   Deutsch.   Med.  Wchnschr.,   1915, 

xli,  696. 
Skoog:     Cerebrospinal  Fluid  Pressure,  Jour.  Am.  Med.  Assn.,  1917,  Ixix,  1064. 


CHAPTER  IV 

PROPERTIP]S  OF  NORMAL  CEREBROSPINAL  FLUID 

The  term  "normal"  as  applied  in  the  literature  to  cere- 
brospinal fluid  is  often  misleading.  The  mere  fact  that 
cerebrospinal  fluid  has  been  removed  from  a  living  person 
is  indicative  of  the  presence  of  some  abnormality  of  the 
nervous  system  that  prompted  the  puncture.  Often  the  bac- 
teriologic  and  qualitative  chemical  tests  on  a  given  specimen 
of  fluid  are  negative,  yet  quantitative  chemical  analysis 
will  shoM^  an  alteration  in  the  chemical  or  physical  chem- 
istry of  the  fluid.  Furthermore,  fluid  removed  postmortem 
can  hardly  be  considered  normal,  for  it  has  usually  under- 
gone marked  chemical  and  physicochemical  changes  be- 
fore examination.  For  instance,  fluid  removed  postmortem 
has  been  shown  by  Myers  to  contain  three  and  one-half 
times  as  much  potassium  oxide  as  fluid  removed  during  life. 
I  also  found  a  marked  difference  between  fluid  removed 
during  life  and  after  death.  In  the  former  case  the  fluid 
was  slightly  alkaline  and  in  the  latter,  distinctly  acid. 
"Normal"  as  applied  to  cerebrospinal  fluid  should,  there- 
fore, be  considered  merely  as  a  relative  term;  the  term 
"nonmeningitic"  perhaps  would  be  still  more  accurate  to 
designate  the  condition  of  the  fluid  where  there  may  be 
some  pathologic  condition  of  the  nervous  system,  such  as 
brain  tumor,  hydrocephalus  or  the  like,  but  no  involvement 
of  the  meninges. 

In  the  discussion  following  in  this  chapter  I  shall  state 
so  far  as  possible  whether  the  cerebrospinal  fluid  under 
discussion  was  withdrawn  during  life  or  postmortem,  and 
whether  it  was  obtained  by  lumbar  or  hj  ventricular  punc- 
ture. I  shall  also  endeavor  to  indicate  the  diagnosis  of 
the  respective  cases  so  that  the  reader  may  be  able  to  form 
an  opinion  regarding  the  type  of  the  fluid  in  question. 

75 


76  CEREBROSPITS^^AL  FLUID 

PHYSICAL  PROPERTIES 

Amount 

The  amount  of  fluid  normally  present  in  tlie  ventricles 
and  in  the  subarachnoid  space  has  been  variously  stated. 
Contugno  found  between  125  and  156  c.c.  in  both;  Magendie 
found  between  62  and  372  c.c;  Luschka  found  only  25  c.c. 
According  to  Magendie,  the  normal  amount  of  cerebro- 
spinal fluid  in  a  medium-sized  man  is  62  c.c.  Of  this  amount, 
Magendie  ssljs,  the  ventricles  contain  from  20  to  30  c.c, 
and  the  subarachnoid  space  of  the  cord  the  greatest  part 
of  the  remainder.  It  may  be  interesting  to  note  that  al- 
though there  is  from  60  to  150  c.c.  of  cerebrospinal  fluid 
present  in  the  subarachnoid  space  and  the  ventricles,  it  is 
generally  inadvisable  and  often  impossible  to  remove  more 
than  10  c.c.  of  fluid  from  a  patient  at  one  sitting. 

Color 

Normal  cerebrospinal  fluid  is  clear  and  colorless,  pro- 
vided no  blood  has  been  removed  with  it  during  the  punc- 
ture. The  fluid  does  not  change  color  upon  standing  if 
it  is  corked  with  a  cotton  plug,  unless,  of  course,  it  has  be- 
come contaminated  by  bacteria  or  moulds,  in  which  case 
the  fluid  becomes  turbid. 

Lack  of  Sediment 

Normal  cerebrospinal  fluid  shows  no  pellicle  or  sediment 
of  any  kind.  This  is  because  of  the  fact  that  the  cell  con- 
tent, as  well  as  the  protein  content,  is  very  small,  and  fibrin 
is  either  entirely  absent  or  present  only  in  very  small 
traces.  The  lack  of  sediment  is  helpful  in  differentiating 
normal  or  nonmeningitic  fluid  from  fluid  in  cases  of  menin- 
gitis, especially  tuberculous,  in  which  the  diagnosis  is  dif- 
ficult because  of  the  clearness  of  the  fluid. 


PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID      /  / 

Pressure 

Observations  on  tlie  pressure  of  normal  cerebrospinal 
fluid  have  given  various  results  in  the  hands  of  different 
workers.  Magendie  found  that  the  pressure  of  the  cere- 
brospinal fluid  is  positive.  Falkenheim  and  Naunyn  claim 
that  it  is  necessary  for  the  maintenance  of  the  blood  circula- 
tion of  the  brain  that  the  cerebrospinal  fluid  remain  at  a 
certain  pressure  and  they  estimate  the  pressure  under  nor- 
mal conditions  to  vary  between  50  and  200  mm.  of  water 
(4  to  16  mm.  Hg)  for  a  child  one  month  to  one  year  of  age 
with  a  correspondingly  higher  pressure  for  an  adult. 
Quincke  gives  40  to  60  mm.  of  water  as  the  normal  pres- 
sure for  children,  and  150  for  adults;  Adamkiewicz  gives 
80  to  100  mm.  of  water,  and  Sicard  gives  200  as  the  normal 
pressure.  Many  factors  are  responsible  for  these  discrep- 
ancies, the  most  important  of  them  being  the  type  of  the 
pressure  apparatus,  the  insertion  of  the  needle,  the  age  of 
the  patient,  the  position  of  the  patient  during  the  puncture, 
the  position  of  the  head,  the  respiratory  movements,  and 
such  external  factors  as  coughing,  sneezing  and  crying. 

(a)  Different  pressure  apparatus  give  different  pressure 
values.  In  some  forms  of  apparatus  fluid  is  lost  and  there- 
fore too  small  values  are  obtained.  (Cf.  Chapter  III.) 
The  position  of  the  needle  is  also  responsible  for  variation 
in  pressure.  A  deeper  insertion  of  the  needle  into  the  canal 
gives  a  higher  pressure  than  a  slight  insertion,  and  vice 
versa. 

(b)  Age  also  plays  a  part  in  the  pressure  of  the  fluid. 
Quincke  found  pressure  in  children  to  be  less  than  that  in 
adults.  He  gives  40  to  60  mm.  water  as  the  pressure  in 
children,  and  150  mm.  water  as  the  pressure  in  adults.  I 
also  found  the  pressure  to  be  lower  in  children  than  in 
adults.  My  figures  showed  a  pressure  variation  of  from  45 
to  90  mm.  water  in  children  in  a  quiet  recumbent  posture 
and  130  to  150  mm.  water  in  adults. 


78  CEREBROSPIXAL  FLUID 

(c)  The  position  of  the  patient  during  puncture  has  a 
marked  influence  on  the  pressure,  the  pressure  in  the  sit- 
ting j)08ition  being  niucli  liiglier  tlian  in  the  recumbent  jdo- 
sition.  Kroenig  found  the  pressure  in  the  lying  posture 
to  be  120  mm.  of  water  and  in  the  sitting  posture  410  mm. 
of  water.  E.  Cotton  and  M.  C.  Salz  found  the  normal  pres- 
sure in  the  recumbent  position  to  be  200  to  230  mm.  of  water 
and  in  the  sitting  position  to  be  400  to  420  mm.  water.  I 
found  the  normal  pressure  in  the  recumbent  position  in 
children  under  ten  to  vary  between  45  and  90  mm.  of  water 
and  in  the  sitting  position  to  vary  between  150  and  230  mm, 
of  water.  In  adults,  in  recumbent  position  the  pressure 
varied  between  130  and  150  and  in  the  sitting  position  be- 
tween 200  and  250. 

(d)  Flexion  of  the  head  on  the  chest  lessens  the  pressure 
and  extension  of  the  head  raises  the  pressure,  the  difference 
between  the  two  varying  from  150  to  230  mm.  of  water. 

'(e)  Magendie  commented  on  the  effect  of  the  respiratory 
movements  on  the  pressure  of  the  fluid.  He  observed  that 
the  cerebrospinal  fluid  showed  movements  corresponding 
to  the  respiration,  the  pressure  falling  during  inspiration 
and  rising  during  expiration.  This  observation  has  been 
confirmed  by  many  workers.  I  have  observed  it  frequently. 
The  variation  between  inspiration  and  expiration,  how- 
ever, is  small,  the  difference  averaging  from  10  to  15  mm. 
of  water. 

(f)  The  relation  between  the  pressure  of  the  cerebro- 
spinal fluid  and  the  pulse  beat  was  pointed  out  by  Falken- 
heim  and  Naunyn.  This  is  noticeable,  however,  only  Avhen 
the  pressure  is  high,  above  300  mm.  of  water. 

(g)  Coughing,  crying,  sneezing  or  any  other  strain  may 
increase  the  pressure  from  50  to  100  mm.  of  water. 

Summarizing,  it  may  be  said  that  the  normal  pressure 
of  the  cerebrospinal  fluid  is  influenced  by  many  factors. 
As  a  general  rule,  however,  the  pressure  varies  from  45  to 
90  mm.  in  children,  and  from  130  to  150  mm.  in  adults. 


PllOPEKTIES    OF    NORMAL    CEREBROSPINAL    FLUID  79 

Table  IV 

Cerebrospinal  Fluid  Pressure  in  Normal  Individuals  Expressed  in 
Millimeters  op  Water 

Author  adui-t  child 

LYING        sitting      LYING        SITTING 

40-60 


Quincke 

150 

Adamkiewicz 

80-100 

Kroenig 

125-150 

410 

Cotton  and  Salz 

200-300 

400-420 

Boveri 

170-200 

Levinson 

130-150 

200-250 

These  figures  are  for  the  recumbent  position.  They  are 
very  much  higher  for  the  sitting  position.  The  withdrawal 
of  several  cubic  centimeters  of  cerebrospinal  fluid  lessens 
the  pressure  temporarily,  but  in  a  very  short  time  it  re- 
turns to  normal.  So  it  frequently  happens  that  when  two 
punctures  are  made  in  one  day,  the  pressure  is  found  to 
be  the  same  in  both  cases. 

Specific  Gravity 

The  specific  gravity  of  normal  cerebrospinal  fluid  varies 
between  l.OOl  and  1.008.  Hoppe  found  the  gravity  in  a 
case  of  spina  bifida  to  be  1.001  and  in  one  case  of  hydro- 
cephalus to  be  1.005.  Halliburton  found  the  gravity  of 
normal  fluid  to  be  1.007  to  1.008,  and  Kafka  found  it  to 
vary  between  1.002  and  1.008.  Zdarek  gives  the  specific 
gravity  of  normal  cerebrospinal  fluid  as  1.0078,  Polanyi  as 
1.012  (15  degrees);  1.007  and  1.005.  Mestrezat  found  it 
to  be  1.0076,  and  Nawratski  found  it  to  be  1.0073  to  1.008. 
In  a  series  of  nonmeningitic  cerebrospinal  fluids  examined 
by  tlie  pyknometer  I  found  the  specific  gravity  to  vary  be- 
tween l.t)0C)4and  1.0070. 

CHEMICAL  COMPOSITION 

In  spite  of  the  large  amount  of  work  on  the  chemical  com- 
position of  the  cerebrospinal  fluid,  there  are  many  funda- 


80  CEREBllOSPINAL  FLUID 

mental  questions  pertaining  to  tlie  chemistry  of  this  fluid 
that  have  not  yet  been  answered.  The  reason  that  our  in- 
formation regarding  the  chemistry  of  cerebrospinal  fluid 
is  not  as  definite  and  as  accurate  as  it  might  be,  is  that 
the  amount  of  fluid  one  is  obliged  to  work  with  under  nor- 
mal conditions  is  usually  so  small  (5  to  10  c.c.)  that  it  hardly 
permits  any  quantitative  separations. 

It  is  but  recently  that  microchemical  methods  have  been 
devised  for  body  fluids,  and  even  now,  with  improved  meth- 
ods, it  is  hardly  possible  to  make  an  entire  quantitative 
analysis  on  one  normal  specimen  of  cerebrospinal  fluid. 
This  scarcity  of  fluid  necessitates  working  on  one  chemical 
substance  at  the  time  or  the  use  of  a  mixture  of  fluids  for 
the  determination  of  the  various  chemical  constituents,  a 
procedure  adopted  by  Mestrezat.  One  can  readily  see  that 
data  gathered  in  this  way  can  not  be  very  accurate,  espe- 
cially since  the  chemical  character  of  the  fluid  is  affected 
by  such  factors  as  the  condition  of  the  patient,  and  the  age 
of  the  fluid.  It  is  surprising  to  note,  however,  that  with  all 
of  the  drawbacks  some  of  the  chemical  determinations  of 
the  very  early  investigators  still  hold  good,  particularly 
the  determinations  of  the  organic  matter,  and  of  the  amount 
of  the  total  solids  and  chlorides. 

I  shall  present  here  data  obtained  from  the  literature, 
following  the  experiments  so  far  as  possible  in  chronologic 
order  to  show  the  evolution  of  chemical  methods  as  ap- 
plied to  cerebrospinal  fluid.  I  shall  give  a  complete  table 
at  the  end  of  the  discussion  showing  the  results  of  the  work 
by  various  authors  on  the  chemistry  of  the  cerebrospinal 
fluid. 

One  of  the  earliest  determinations  of  the  chemical  com- 
position of  cerebrospinal  fluid  was  that  of  Lassaigne  Avho 
examined  the  cerebrospinal  fluid  of  a  horse  after  death. 
The  fluid  was  obtained  for  the  chemist  by  Magendie.  The 
analysis  gave  the  following  composition  per  100  parts: 


PROPErtTlES    OF    NORMAL    CEREBROSPINAL   FLUID  81 

Water     98.180 

Osmazome    1.104 

Albumin     0.033 

Sodium  Chloride 0.610 

Sodium  bicarljonate    0.060 

Phosphate  and  traces  of  calcium 

carbonate 0.009 

Lassaigne  could  not  find  any  soluble  phosphates  in  the 
liquor. 

The  same  author  examined  the  cerebrospinal  fluid  of  an 
old  woman  and  found  the  following  per  100  parts: 

Water    98.564 

Osmazome    0.474 

Albumin  0.088 

Sodium  and  potassium  chloride....   0.801 
Animal    matter    and    free    calcium 

phosphate    0.036 

Sodium  carbonate  and  calcium  phos- 
phate    0.017 

Among  the  early  workers  in  this  field  was  Hoppe.  He 
made  a  chemical  analysis  in  two  cases  of  spina  bifida  and 
three  cases  of  internal  hydrocephalus.  In  one  case  of  spina 
bifida,  he  removed  22  to  35  c.c.  of  cerebrospinal  fluid  at  a 
sitting.  (The  author  unfortunately  does  not  give  the 
method  he  employed  in  the  removal  of  the  fluid.)  He  found 
the  fluid  very  alkaline.  (Here  again  the  author  does  not 
say  what  indicator  he  used,  or  how  long  after  removal  of 
the  fluid  from  the  body,  he  examined  it).  On  heating,  the 
fluid  became  slightly  turbid,  but  on  addition  of  acetic  acid, 
flocculi  appeared.  The  fluid  reduced  copper  oxide  and 
gave  the  following  quantitative  results  in  grams  per  1000: 

FIRST  SECOND  THIRD 

PUNCTURE  PUNCTURE  PUNCTURE 

Albumin  1.62  2.64  2.46 

Water  extractive  0.70  0.35  0.42 

Alcohol  extractive  1  q  g-r  2,48  2.23 

and  soluble  salt   J  '  7.52  8.21 

Insoluble  salt  0.25  0.15  0.28 

Giving — 

Dry   substance  12.51  13.12  13.28 

Water  987.49  986.88  986.72 


82  CEREBROSPINAL  FLUID 

From  the  second  ease  of  spina  bifida  the  author  obtained 
500  c.c.  of  cerebrospinal  fluid,  in  the  first  puncture,  and 
435  c.c.  in  the  second  puncture.  The  reaction  of  the  fluid  in 
this  case  was  also  stated  to  be  alkaline.  On  boiling,  very 
little  if  any  turbidity  occurred.  On  the  addition  of  acetic 
acid  slight  flocculency  occurred.  Quantitative  analysis 
showed  the  following  in  grams  per  1000: 


FIRST    PUNCTURP, 

SECOND    PUNCTURE 

Albumin 

0.25 

0.55 

Extractives 

2.30 

2.00 

Soluble  salts 

7.67 

7.20 

Insoluble  salts 

0.45 

0.45 

Dry  Substance 

10.67 

10.20 

One  case  of  hydrocephalus  in  a  five-month-old  girl  gave 
Hoppe  the  following  in  grams  per  1000:  albumin  0.70,  ex- 
tractives, 1.57,  soluble  salts  7.67,  insoluble  salts  0.53,  giv- 
ing dry  substance  10.47. 

Another  case  of  hydrocephalus  gave  Hoppe  the  follow- 
ing in  grams  per  1000:  albumin  11.79,  alcohol  extractives 
0.84,  water  extract  0.48,  soluble  salts  7.54,  insoluble  salts 
0.35,  and  dry  matter  20.99.  It  is  evident,  however,  from 
the  author's  description  of  the  fluid  of  the  last  case  which 
he  says  was  of  a  greenish  yellow  color  and  showed  a  large 
sediment,  absence  of  sugar  and  numerous  cells,  that  the 
case  was  one  of  meningitis. 

Halliburton  also  was  one  of  the  first  to  study  the  chem- 
ical composition  of  cerebrospinal  fluid.  He  found  no  coag- 
ulation of  the  fluid  at  56°  C.  and  no  fibrin  on  the  addition 
of  serum  or  fibrin  ferment.  He  found  further  that  practi- 
cally all  the  protein  present  in  the  cerebrospinal  fluid  was 
precipitated  by  saturation  wdtli  magnesium  sulphate.  The 
analysis  of  cerebrospinal  fluid  in  a  number  of  cases  gave 
Halliburton  the  following  results  in  parts  per  1000: 


PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID 


CASE     1. 

CASE    2. 

CASE    3. 

FEMALE AGE    19 

CHILD — AGE 
DAYS 

11 

CHILD — AGE     13 
WEEKS 

FIRST   TAPPING 

FOUKTH   TAPPING 

Water 

989.75 

989.877 

991.658 

Solids 

10.25 

10.123 

8.342 

Proteins 

0.842  . 

0.602 

0.199 

Extractives 

0.631 

3.028 

and 

9.626 

Salts 

7.890 

5.115 

It  is  interesting  to  note  in  this  connection  the  part  taken 
by  Halliburton  in  the  discussion  concerning  the  nature  of 
the  reducing  substance  in  the  cerebrospinal  fluid.  As  early 
as  1852,  Deschambs  and  Bussy  described  the  presence  of  a 
copper-reducing  substance  in  cerebrospinal  fluid,  a  finding 
corroborated  by  numerous  other  workers.  However,  the 
character  of  this  substance  has  been  made  the  sijbject  of  a 
great  deal  of  discussion.  Quincke,  Comba,  Friedenthal,  Pan- 
zer and  others  considered  it  to  be  a  dextrose.  Halliburton 
however,  supported  by  Mathien,  Gauthies  and  others  ex- 
pressed the  view  that  the  reducing  substance  was  pyro- 
catechin.  Langstein  thought  that  a  portion  of  the  reducing 
substance  was  galactose  and  Dubos  believed  that  it  was  a 
xanthine  body.  Recent  investigations  have  settled  this  con- 
troversy, the  phenylhydrazin,  the  fermentation  test,  and  the 
polariscope  definitely  proving  its  identity  as  a  dextrose. 
Even  Halliburton  now  admits  that  this  reducing  substance 
is  a  dextrose. 

The  early  investigations  on  the  chemistry  of  cerebro- 
spinal fluid  were  made  on  cases  of  hydrocephalus  or  spina 
bifida.  Of  recent  years  some  work  has  been  done  on  the 
chemistry  of  cerebrospinal  fluid  of  comparatively  normal 
persons.  The  work  of  Mestrezat,  of  Leopold  and  Bern- 
hard  deserves  special  attention  in  this  connection.  There 
are  many  additional  facts  on  the  chemical  constituents  of 
the  cerebrospinal  fluid  scattered  throughout  the  literature, 
some  of  which  are  included  in  the  table  at  the  end  of  the 
chapter. 


84  CEREBRPSPINAL  FLUID 

Mestrezat,  in  a  series  of  analyses,  found  the  following 
chemical  composition  of  cerebrospinal  fluid,  expressed  in 
grams  per  1000  parts:  fixed  matter  10.65  to  11.00,  with  an 
average  of  10.93 ;  organic  matter  1.75  to  2.65  with  an  aver- 
age of  2.13;  mineral  matter  8.50  to  9.00,  with  an  average 
of  8.80;  protein  0.13  to  0.30  with  an  average  of  0.18.  He 
found  no  fibrinogen,  no  albumose  or  peptones,  or  nucleo- 
protein  and  nmcin.  He  also  noted  the  absence  of  cholin, 
and  cholesterol  (or  only  a  very  small  trace  of  choles- 
terol). Amino  acids  were  present  on  the  average  in  the 
amount  of  0.010,  urea  on  the  average  of  0.06,  varying  be- 
tween the  extremes  of  0.03  and  0.10.  The  presence  of  am- 
monia was  questionable,  total  nitrogen  was  found  on  the 
average  of  0.197,  with  the  extremes  of  0.196  to  0.198;  sugar 
(reducing  tnatter  and  glucose)  on  the  average  of  0.53,  with 
the  extremes  0.48  to  0.58.  Total  organic  acids  were  pres- 
ent on  an  average  of  0.30.  There  was,  however,  no  acetone 
found;  chlorides  on  the  average  of  7.32,  with  the  extremes 
of  7.25  to  7.40;  total  phosphorus  on  the  average  of  0.030 
in  terms  of  P2O5  with  the  extremes  of  0.029  to  0.031;  in- 
organic phosphorus  on  the  average  of  0.012  in  terms  of 
P2O5 ;  organic  phosphorus  on  the  average  of  0.018  in  terms 
of  P2O5 ;  total  sulphur  on  the  average  of  0.056  ^\^th  the  ex- 
tremes of  0.028  to  0.071 ;  inorganic  sulphur  on  the  average 
of  0.010  in  terms  of  SO3 ;  organic  sulphur  on  the  average  of 
0.046  in  terms  of  SO3;  nitrates  on  the  average  of  0.009; 
no  nitrites;  sodium  4.346  as  NaaO;  potassium  0.251  as  K2O; 
ratio  of  KoO/NaaO  1/17.3 ;  calcium  0.095  as  CaO ;  magnesium 
0.050  as  MgO. 

Leopold  and  Bernhard  determined  the  nonprotein  nitro- 
gen of  normal  cerebrospinal  fluid.  They  found  that  the 
nonprotein  nitrogen  varied  between  17  and  26  mg.  per  100 
c.c.  of  cerebrospinal  fluid  the  average  amount  being  21  mg. 
The  urea  varied  between  7  and  13.5  mg.  per  100  c.c.  of  fluid, 
the  average  amount  being  9.9  mg.  The  creatinine  varied 
between  0.7  and  1.5  mg.  per  100  c.c.  of  fluid,  the  average 


PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID      85 

amount  being  0.9  mg.  The  sugar  content  varied  between 
0.07  and  0.1  per  cent,  the  average  content  being  0.07  per 
cent. 

My  own  work  on  the  chemistry  of  cerebrospinal  fluid  is 
concerned  mostly  with  the  constituents  that  have  or  were 
expected  to  have  a  direct  bearing  on  the  differential  diag- 
nosis and  pathogenesis  of  various  diseases,  including  the 
protein  content,  the  organic  index,  the  sugar  content,  lactic 
acid,  and  urea,  among  the  organic  constituents,  and  the 
chlorides,  the  phosphates  and  CO2  among  the  inorganic 
constituents.  The  organic  index  was  determined  by  the 
permanganate  method  of  Meyerhofer,  taking  the  amount 
of  permanganate  required  to  oxidize  the  organic  sub- 
stance in  the  cerebrospinal  fluid  as  an  index  (the  method 
will  be  described  in  detail  in  Chapter  VI).  The  protein 
was  determined  by  precipitating  the  cerebrospinal  fluid 
with  equal  amounts  of  5  per  cent  trichloracetic  acid,  wdth 
a  pinch  of  kaolin,  filtering  off  the  inorganic  constituents 
and  determining  the  nitrogen  in  the  sediment  by  the  Kjel- 
dahl  method  and  multiplying  by  the  factor  K  x  6.25.  The 
sugar  was  determined  by  the  Kowarsky  method  and  also  by 
the  Lewis  and  Benedict  method.  Occasionally,  the  Epstein 
microchemical  method  was  used.  Urea  was  determined  by 
the  Folin  method,  acetone  was  determined  qualitatively  by 
the  sodium  nitroprusside  method.  Lactic  acid  by  Uf- 
felmans  reagent,  noting  the  drops  of  cerebrospinal  fluid  re- 
quired to  change  the  reagent  to  a  canary  yellow.  The 
chlorides  were  determined  by  the  Seelman  method,  the 
phosphates  by  the  uranium  acetate  method  and  the  CO2  by 
the  Van  Slyke  method  for  the  determination  of  alkali 
reserve  and  then  calculating  out  the  CO2  from  the  results 
obtained,  or  the  alkali  reserve  was  obtained  by  methyl  red 
titration.  I  should  like  to  emphasize  here  that  the  fluid  has 
been  nomncningitic,  but  nevertheless  not  always  absolutely 
normal.  Tables  V,  VI,  and  VII  show  some  of  the  average 
findings  in  nonmeningitic  fluids. 


86 


CEREBROSPINAL  FLUID 

Table  V 
The  Permanganatk  Index  in  Nonmeningitic  Fluid 


DIAGNOSIS 


permanganate   index 
first  tube       subsequent  tubes 


1 

Typhoid 

1.8 

1.6 

1.7 

2 

Pneumonia 

1.3 

1.3 

3 

Pneumonia 

1.4 

1.2 

1.0 

4 

Tetany 

1.3 

1.2 

5 

Epilepsy 

1.3 

1.1 

6 

Grippe 

l.o 

1.4 

Table  VI 
Sugar  Content  in  Nonmeningitic  and  Nonluetic  Cases 


sugar 

other 

NO. 

diagnosis 

content 

TESTS 

1 

Alimentary 

0.116 

Chemical  and 

Intoxication 

bacteriologic 
tests  negative 

2 

Pneumonia  with 

0.108 

All  tests 

meningism 

negative 

3 

Insanity 

0.108 

Negative 

4 

Uremia 

0.067 

Negative 

5 

Insanity 

0.058 

Negative 

6 

Insanity 

0.048 

Negative 

7 

Otitis  Media 

0.032 

Negative 

8 

Erysipelas 

0.144 

Negative 

9 

Renal  Insufficiency 

0.048 

Negative 

10 

Pneumonia  and 

meningism 

0.032 

Negative 

11 

Pneumonia 

0.088 

Negative 

12 

Brain  tumor 
also   right 

ovarian    cyst 

0.116 

Negative 

13 

Cerebral   spastic 

paralysis 

0.06 

Negative 

14 

Hydrocephalus 

0.104 

Negative 

15 

Insanity 

0.118 

Negative 

16 

Hematogenous  .laundice 

0.12 

Negative 

17 

Epilepsy — had  menin- 

gitis one  year  previously 

0.068 

Negative 

18 

Encephalitis, 

0.048 

Negative 

19 

Cerebellar  tumor,  re- 

peated convulsions 

0.072 

Negative 

20 

Brain  tumor 

0.068 

Negative 

21 

Multiple  sclerosis 

0.148 

Negative 

22 

Localized  encephalitis 

recovered. 

0.140 

Negative 

(Cont'd  p.   87) 

PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID 


87 


Table  VI— Cont'd 
Sugar  Content  in  Nonmeningitic  and  Nonluetic  Cases 


DIAGNOSIS 


sugar 
content 


OTHER 

tests 


23 

Acidosis  (?) 

0.104 

Negative 

24 

Normal 

0.086 

Negative 

25 

Normal 

0.09 

Negative 

26 

Normal 

0.106 

Negative 

27 

Normal 

0.064 

Negative 

28 

Normal 

0.088 

Blood  sugar— 0.088 

Negative 

29 

Normal 

0.108 

Negative 

30 

Normal 

0.064 

Negative 

31 

Normal 

0.07 

Negative 

Table  VII 
Chlorides  in  Nonmeningitic  Fluid 


diagnosis 


chlorides 
(in  gms.  per  100  c.c.) 


Psychosis 

0.74 

Alcoholic  psychosis 

0.72 

Alcoholic  psychosis 

0.60 

Meningism 

0.72 

Pneumonia 

0.60 

Psychosis 

0.68 

Psychosis 

0.70 

Tertiary  lues 

0.75 

Chorea 

0.70 

Table  VIII 
Urea  in  Nonmeningitic   Fluid 


no. 

diagnosis 

UREA   IN  GM.  PER  100  C.C. 

1 

Psychosis 

0.032 

2 

Meningism 

0.090 

3 

Psychosis 

0.042 

4 

Psychosis 

0.064 

5 

Meningism 

0.070 

6 

Psychosis 

0.043 

The  amount  of  CO2  in  the  cerebrospinal  fluid  varied  in 
my  cases  with  the  time  the  fluid  has  been  standing  after  re- 
moval from  the  body.    The  longer  it  stands  before  exami- 


OO  CEREBROSPINAL  FLUID 

nation  the  less  CO2  it  contains.  In  fluid  examined  immedi- 
ately after  withdrawal  from  the  l)ody,  the  CO2  varies  be- 
tween 0.110  gm.  and  0.124  gm.  per  100  c.c.  In  fluid  exam- 
ined five  to  six  hours  after  it  has  been  removed  from  the 
body,  the  CO2  varies  between  0.098  gm.  and  0.106  gm.  per 
100  c.c.  Table  IX  shows  some  of  the  amount  of  CO2  ob- 
tained in  volumes  per  cent. 

Table  IX 

Total  Carbonate  of  Noxmenixgitic  Cerebrospixal  Fli-id  axd  Its 
Relatiox  to  the  H-Iox  Coxcextratiox 

total    carbonate    in 
xo.  dl\gx0sis  ph 

volume  per  cent 


1 

Dementia   Precox 

7.-4 

58.75 

2 

Psychosis 

7.4 

55.72 

<  I 

<  ( 

7.7 

51.52 

3 

Cerebrospinal  Lues 

7.5 

55.72 

I  i 

<  c 

7.6 

54.83 

4 

Psychosi3 

7.4 

57.54 

<  ( 

<  < 

8.1 

50.47 

5 

Tabes 

7.4 

63.68 

<  ( 

t  ( 

8.1 

54.08 

6 

Chorea 

7.5-7.6 

63.0 

I  < 

1 1 

8.1 

52.48 

7 

Encephalitis 

7.7 

51.3 

Lactic  acid  was  present  in  traces.  It  took,  as  a  rule,  15 
to  20  drops  of  cerebrospinal  fluid  to  change  the  color  of  5 
c.c.  of  Uffelman's  reagent  to  canary  yellow.  Acetone  was 
negative  in  all  nonmeningitic  fluid,  so  was  also  ammonia. 

Crystallization 

I  evaporated  a  number  of  specimens  of  cerebrospinal 
fluid,  after  precipitating  and  filtering  off  the  protein.  The 
resultant  crystals  (Figs.  17  and  18)  resemble  those  of  so- 
dium chloride  (Fig.  19)  in  most  resjiects. 

When  we  now  examine  cerebrospinal  fluid  for  the  con- 
stituents it  contains  we  find  the  following  amounts:  water, 
98.60  to  99.124  per  cent;  solids,  0.876  to  1.631  per  cent.  Of 
the  solids,  0.175  to  0.265  per  cent  is  organic  matter  and  the 


PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID 


89 


rest  mineral  matter.    The  organic  matter  is  made  up  princi- 
pally of  protein,  sugar  and  urea.     Protein  is  present  in 
amounts  varying  between  0.013  and  0.07 ;  sugar  is  present 
in  amounts  varjdng  between  0.032  and  0.144  per  cent. 
The  bulk  of  the  inorganic  matter  consists  of  chlorides  and 


c  " 

Fig.   17. — Crystallization   of   nonineningitic  cerebrosi)inal   fluid. 
A.  Crystals  obtained   after   the  protein  has  been   removed   from   the   fluid   by   precipita- 
tion and  the  filtrate  evaporated  on  steam  bath.      (Natural  size.) 
R.   Same  fluid  .showing  the  crystals.      (Magnified  24  times.) 

C.  Clump  of  crystals  of  same  fluid.      (Magnified  45   times.) 

D.  Single  crystal.     (Magnified  45  times.) 


90 


CEREBEOSPINAL  FLUID 


Fig.   18. — Crystals   of   evaporated   nonnieningitic   cerebrospinal    fluid.      (Magnified   24 

diameters.) 


Fig.   19. — Crjstals    of   sodium   chloride   in  a    1    per  cent  solution   of   dextrose.      (Magnified 

24   diameters.) 


PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID 


91 


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92 


CEREBROSPIXAL  FLUID 


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PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID 


93 


bicarbonates,  the  chlorides  being  present  in  amounts  vary- 
ing between  0.60  and  0.74  per  cent. 

Both  of  these  constituents  are  present  in  much  greater 
quantities  than  potassium,  calcium  or  magnesium. 

It  is  interesting  to  compare  the  chemical  composition  of 
the  cerebrospinal  fluid  with  that  of  other  body  fluids,  not- 
ably blood,  lymph,  and  aqueous  humor.    In  comparing  the 

Table    XI 
Chemical  Composition  of  Cerebrospinal  Fluid  Compared  with  That  of 

Blood 


blood   serum 

cerebrospinal 

OF  a  man  25 

constituent 

FLUID   in   GM. 

YEARS    OLD 

per  1000 

(by    SCHMIDT) 
IN   GM.   PER  1000 

Water 

996.67 

908.84 

Dry  substance 

10.93 

91.16 

Organic  Substance 

2.13 

82.58 

Albuminoid 

0.18 

Albumose  and  Peptones 

Amino   Acids 

0.010 

0.0099 

Urea 

0.06 

0.10-0.30 

Ammonia 

? 

0.04-0.010 

Reducing  Substance 

0.53 

1.0-1.50 

(Glucose) 

Chloride   (as  Sodium 

7.32 

5.86 

Chloride) 

Direct  alkalinity  as  Na^CO 

1.25 

3.26 

Ashes 

8.80 

8.574 

Na^O 

4.346 

3.438 

K,0 

0.251 

0.317 

CaO 

0.095 

0.162 

MgO 

0.050 

0.073 

Fe,03 

0.002 

? 

PA  (total) 

0.030 

0.375 

SO3  (total) 

0.056 

0.130 

CO,  (of   ashes) 

0.550 

0.90-130 

CI 

4.448 

3.556 

Ratio  of  K„0  to  Na^O 

1/17.3 

1/10.8 

chemical  composition  of  the  cerebrospinal  fluid  with  that  of 
the  blood  we  find  that  they  both  contain  practically  the  same 
constituents,  and  that  some  of  the  constituents  are  present 
in  the  same  amounts  in  both.  This  is  particularly  true  of 
sugar  and  urea.    I  often  found  sugar  to  be  present  in  the 


94  CEREBROSPINAL  FLUID 

same  amounts  in  both  the  fluid  and  in  the  blood.  CuUen  and 
Ellis  found  a  difference  of  less  than  2  mg.  per  1000  c.c,  in 
the  amounts  of  urea  in  the  fluid  and  the  blood,  in  63  per 
cent  of  their  determinations.  The  urea  content  of  the  fluid 
varied  from  22  to  46  mg.  and  that  of  the  blood  serum  be- 
tween 20  to  42  mg. 

The  other  chemical  constituents,  on  the  contrary,  are 
present  in  much  smaller  proportions  in  the  fluid  than  in 
the  blood.  The  protein  in  the  fluid  varies  between  0.013 
and  0.07  whereas  that  in  the  blood  plasma  varies  between 
6.95  and  7.76  per  cent.  The  calcium  content  of  the  fluid,  ac- 
cording to  Halverson  and  Bergeim,  is  only  one-half  that  of 
the  blood,  the  calcium  in  the  fluid  being  0.005  gm.  per  100 
c.c,  while  that  in  the  blood  plasma  or  serum  is  0.01  per  100 
c.c.  Table  XI  of  Mestrezat  shows  the  chemical  constit- 
uents of  the  cerebrospinal  fluid  and  the  blood. 

PHYSICOCHEMICAL  PROPERTIES  OF  NORMAL 
CEREBROSPINAL  FLUID 

There  is  no  line  of  scientific  investigation  where  so  many 
factors  enter  into  the  results  obtained  as  in  physicochemical 
determinations.  Temperature,  barometric  pressure  and  es- 
pecially the  time  the  fluid  has  been  standing  before  it  is 
examined  count  a  great  deal.  So  it  comes  that  while  the 
chemical  data  found  in  the  literature  of  several  years  ago 
are  in  the  main  confirmed  by  newer  investigations,  some  of 
the  older  physicochemical  data  are  found  incorrect  when 
newer  methods  are  used,  and  when  the  various  factors 
influencing  physicochemical  findings  are  taken  into  con- 
sideration. Especially  is  this  true  with  regard  to  the  reac- 
tion of  the  cerebrospinal  fluid  and  the  alkali  reserve. 

Specific  Gravity 

The  specific  gravity  of  normal  cerebrospinal  fluid  to 
which  I  have  already  referred  in  the  discussion  of  the  phys- 
ical properties  of  normal  cerebrospinal  fluid,  belongs  also 


PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID      95 

in  a  discussion  on  physicoehemieal  properties  of  the  fluid, 
since  specific  gravity  forms  the  basis  of  many  physico- 
chemical  constants.  The  specific  gravity  varied  in  my 
cases  between  1.0064  and  1.0070,  and  according  to  other 
authors,  it  varies  between  1.001  and  1.008. 

Viscosity 

Polanyi  found  the  viscosity  to  vary  between  1.020  and 
1.027  at  a  temperature  of  38°  C,  taking  the  viscosity  of 
water  as  1.  I  examined  the  viscosity  of  several  cerebro- 
spinal fluids,  by  means  of  the  Ostwald  apparatus,  and  found 
it  to  vary  between  1.0424  and  1.0489  compared  to  water. 

Conductivity 

Polanyi  examined  the  conductivity  of  the  cerebrospinal 
fluid  of  hydrocephalus  and  found  it  to  be  0.01136;  0.01280; 

1 

0.01527;  and  0.01452  at  20°  C.     (Formula  ). 

Ohm  X  Cm. 
My  examination  gave  the  conductivity  as  .01513,  .01365, 
and  .01513  at  25°  C. 

Surface  Tension 

Polanyi  found  the  surface  tension  to  be  7.35,  7.15,  7.16 
and  7.20  dynes  at  20°  C. 

Freezing  Point 

Grenet  found  the  freezing  point  of  normal  cerebrospinal 
fluid  to  be  -.38°  to  -.56°  C.  Quincke  found  it  to  be  -.56° 
to  -.75°.  Polanyi  found  it  to  be  -.566°,  -.570°,  -.678°, 
-.583°.  Mott  found  it  to  be  -.51°  to  -.56°.  Mestrezat  found 
the  average  to  be  -.576°,  with  the  extremes  varying  be- 
tween -.57°  and  -.59°.  My  findings  showed  the  freezing 
point  to  vary  between  -.56°  and  -.58°.  In  general  it  must 
be  said  here  also  that  the  interval  between  the  removal  of 


96  CEEEBPtOSPIiSrAL  FLUID 

the  cerebrospinal  fluid  from  the  body,  and  the  time  of  the 
examination  is  a  great  factor ;  although  the  variation  in  the 
freezing  point  on  standing  is  not  nearly  as  much  as  is  the 
case  with  H-ion  concentration,  or  with  the  alkali  reserve. 

Refractometric  Index 

Polanyi  found  the  refractometric  index  to  be  1.3499  at 
23°  C,  1.33516  at  21°  C,  1.33579,  at  20.3°  C,  and  1.33554  at 
20°  C.    I  found  it  to  be  1.73516  at  23°  C. 

Reaction  of  Normal  Cerebrospinal  Fluid 

All  through  the  older  writings,  the  statement  is  found 
that  the  cerebrospinal  fluid  is  alkaline  in  reaction,  the  al- 
kalinity being  given  as  a  rule  as  half  that  of  the  blood. 
Cavazzani  examined  the  fluid  of  two  cases  of  hydroceph- 
alus, and  found  a  neutral  reaction.  Concetti  found  the  fluid 
alkaline  three  times,  and  weakly  alkaline  four  times.  Von 
Jaksch  found  the  alkalinity  to  equal  20  c.c.  of  n/10  acid 
solution. 

Kafka  used  n/10  HCl  and  cochineal  as  an  indicator,  and 
found  that  on  an  average,  20  c.c.  of  acid  was  necessary  to 
neutralize  100  c.c.  of  fluid.  According  to  Mott,  the  alkalin- 
ity of  the  fluid  corresponds  to  0.1  per  cent  of  sodium  hy- 
drate. 

Of  late,  the  entire  conception  of  the  reaction  of  body 
fluids  has  changed  due  mainly  to  the  work  of  Michaelis, 
Sorenson,  Henderson  and  Van  Slyke.  The  reaction  of  body 
fluids  is  now  spoken  of  in  terms  of  hydrogen  and  hydroxyl 
ions,  Avhicli  is  expressed  either  in  the  terms  of  hydrogen- 
ion  concentration,  or  in  terms  of  Ph,  the  latter  term  indi- 
cating the  negative  exponent  of  the  hydrogen-ion  concen- 
tration, for  instance  Ph  7.1  =  1  x  lO'^X.  The  H-ion  concen- 
tration can  be  determined  in  a  number  of  ways,  the  most 
important  of  which  are  the  compensation  method  of  Mich- 
aelis or  of  Hildebrandt,  and  the  indicator  method  of  Sor- 
enson.    Practicallv  all  of  these  methods  have  been  used 


PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID      97 

recently  for  the  study  of  the  cerebrospinal  fluid.  The  re- 
sults, however,  have  not  been  uniform.  Bisgaard  exam- 
ined the  fluid  against  a  borate  mixture,  5.7  plus  HCl, 
and  found  that  the  fluid  was  more  acid  than  the  borate 
mixture.  Polanyi  determined  the  H-ion  concentration 
of  one  fluid  drawn  from  a  case  of  hydrocephalus,  by  the 
compensation  method  with  the  use  of  the  Farkas-Szilisch 
electrode.  He  found  the  H-ion  concentration  to  be  9.084 
X  10.  Hurwitz  and  Tranter,  who  used  the  Levy  Rown- 
tree-Marriott  standards,  found  the  Ph  of  normal  fluids 
to  vary  between  8.15  and  8.30  with  an  average  of  8.26,  this 
being  somewhat  lower  when  the  fluid  was  dialyzed,  the 
average  then  being  8.11.  Weston  found  the  dialyzed  fluid 
to  vary  between  7.9  and  8.3  with  an  average  of  8.12. 

I  have  examined  the  H-ion  concentration  in  over  four 
hundred  normal  cerebrospinal  fluids,  or  to  be  more  accurate, 
fluid  from  cases  that  proved  to  be  nonmeningitic  in  char- 
acter. The  series  includes  cases  of  nephritis,  gastrointes- 
tinal intoxication,  pneumonia,  paresis,  alcoholic  psychosis, 
dementia  precox,  brain  tumor,  epilepsy  and  many  other  con- 
ditions. I  used  the  methods  of  Michaelis  and  Hildebrandt 
for  the  determination  of  old  fluids  and  the  Levy-Rowntree- 
Marriott  method,  or  an  indicator  corresponding  to  this 
method,  in  fresh  fluid.  I  found  that  when  the  fluid  is  ex- 
amined immediately  after  its  withdrawal  from  the  body,  the 
H-ion  concentration  expressed  in  terms  of  Ph  ranges  from 
7.4  to  7.6.  In  only  two  cases  have  I  found  an  H-ion  concen- 
tration of  fresh  fluid  to  be  7.7.  However,  if  the  fluid  has 
been  standing  a  short  while,  the  reaction  changes  very 
quickly  toward  the  alkaline  side.  As  a  rule,  standing  half  an 
hour  changes  the  reaction  to  a  Ph  of  7.5  to  7.6;  standing  one 
hour  changes  the  reaction  to  a  Ph  of  7.7;  standing  two 
hours  changes  it  to  7.9  or  8.0.  From  two  hours  on,  the 
change  in  the  reaction  toward  the  alkaline  side  is  rather 
small,  some  fluids  changing  in  twelve  hours  to  8.1,  and  re- 
maining at  this  concentration  no  matter  how  long  it  stays; 


98 


CEREBROSPINAL  FLUID 


Table  XII 
H-ioN  Concentration  of  Normal  Cerebrospinal  Fluid  by  Other  x\uthors 


AUTHOR 

MET]  ion 

EMPLOYED 

Pa 

FRESH                                       OLD 

UEMAIIKS 

Cavazzaui 

Tartaric 
acid 

Neutral 
Interval  of  standing  not  in- 
dicated. 

2    cases    of     hydro- 
cephalus    also     dogs 

Concetti 

Alkaline     3     times,     weakly 
acid  1  time. 

Interval  of  standing  not  in- 
dicated. 

Myers 

Litmus 

Phenol- 
phthalein 

Neutral  or  faintly  alkaline 

Bisgaard 

Less  than 
8.1 

Kopetzky 

Litmus 

Plienol- 
phthalein 

Less  than  8.0 

Turner 

Acid 

Fluid  in   stoppered 
bottles         retained 
acidity 

Fluid  in  imstopper- 
cd   bottles    became 
.  alkaline 

Polanyi 

Farkas- 
Szilisch 
electrode 

Levy- 
Ro\vn  tree- 
Marriott 
method 

9.0 

Hurwitz 

and 
Tranter 

8.15 
8.30 
average- 

8.1 

Weston 

Levy- 
Rowntree- 
Marriott 
method 

79-8.3 
average- 
8.12 

Felton, 
Hussey 

and 
Bayne- 
Jones 

Levy- 
Rowntree- 
Marriott 
method 

7.7-7.9 

8.6 

other  fluids  elianging  to  8.3  or  even  8.6  in  course  of  twenty- 
four  hours  or  longer. 

In  Table  XI,  I  give  the  ll-ion  concentration  in  some  of  my 
cases  showing  average  results,  indicating  the  method  used 
by  the  letters  a,  b,  c;  "a"  represents  the  gas-chain  method, 
"b"  the  alkalinized  phenolphthalein  compared  to  the 
Sorenson  standards,  and  "c"  the  Levy-Rowntree-Marriott 
indicator  compared  to  the  standard  colorimetric  tubes. 
A  typical  change  in  the  H-ion  concentration  is  illustrated 


PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID      99 

in  the  curve  sho\^^l  in  Fig.  20.  The  results  obtained  by 
phenolphthalein  compared  to  the  Sorenson  standards,  are 
often  marked  with  an  additional  +  and  -  signs.  This  means 
that  Ph  of  the  cerebrospinal  fluid  was  liigher  or  low^er  than 
the  figure  given,  but  how  high  or  how  low  was  not  deter- 
mined. 

These  findings  have  been  so  constant  that  I  believe  we 
can  account  for  the  high  Ph  obtained  in  normal  cerebro- 
spinal fluid  by  the  authors  quoted.     They  examined  the 


8.1 

T-':::,:""::'"  ";::: ';_: 

'_ 

a.i 

^^^^--^ 

"^^^^^^ 

»i 

^ 

S.a 
1.1 

1.1 

r> 

M 

T3 

-^ 

— / 

-— 

/     ' 

1     J 

'M««i         »^         3         H         S        b        7         g         1         Kt        11        <i                                          ' 

Kig.  20. — Average   change  in   the   ll-ion  concent ratiuu   uf   n-jnnicningitic    lluid   on   standing. 

fluid  after  it  had  been  standing  for  some  time,  which 
naturally  gave  a  very  low  H-ion  concentration,  or  a  liigh 
Ph.  Interesting  in  this  connection  is  the  work  of  John 
Turner  who  not  only  knew  of  the  high  H-ion  concentration 
of  the  fluid,  but  was  also  aware  of  the  fact  that  the  concen- 
tration changes  on  standing.    To  quote  him: 

"In  all  the  cases  of  this  series  and  in  twenty  examined 
fifteen  years  ago,  I  have  obtained  an  alkaline  reaction 
(and  not  amphoteric)  to  litmus  paper,  but  with  phenol- 
phthalein the  great  majority  have  an  acid  reaction.    The  de- 


100 


CEREBROSPINAL  FLUID 


Table  XIII 
H-IoN   Concentration   of  Nonmeningitic   Spinal  Fluid 


diagnosis 

Ph 

CASE 

Immediate 

J^  Hour 

1  Hour 

2  Hours 

1 

Little's  disease 

2 

3 

4 

G  astro-enteritis 

5 

g 

Endarteritis 

7 

8 

Brain  tumor 

g 

Tic             

8  0     (b) 

10 

8.0     (b) 

11 

Delirium  tremens 

12 

General  paresis 

13 

14 

Tubercle  of  brain 

Juvenile  paresis 

7.4     (b) 
7.4     (b) 

15 

16 

7.4 +  (b) 
7.4-l-{b) 

17 

General  paresis 

18 

19 

7.5      (c) 

7.4      (c) 

20 

21 

7.5      (c) 

22 

C    Sp    Lues  ? 

7.9      (C) 
7.7      (c) 
7.7     (c) 

23 

24 

25 

7.5  (c) 

7.6  (c) 
7.5      (c) 
7.5      (c) 

26 

27 

28 

29 

8.0     (c) 

30 

8.0     (b) 

31 

7.4      (c) 

7.4  (c) 
7.7      (c) 

7.5  (c) 
7.4      (c) 

7.4  (c) 

7.5  (c) 
7.5      (c) 

7.4  (c) 

7.5  (c) 
7.4      (c) 
7.4      (c) 

7.4  (C) 

7.5  (c) 
7.4      (c) 

7.4      (c) 

7.5      (c) 

7.9      (c) 

32 

General  paresis 

33 

34 

35 

36 

37 

38 

39 

40 

General  paresis 

41 

7.6      (c) 
7.8     (c) 

Mixture 

42 

43 

Mixture 

Mixture 

44 

7.7      (c) 

Mixture 

7.4      (c) 

45 

46 

Pneumonia 

7.7      (C) 
7.4     (c) 

7.4  (c) 

7.5  (c) 
7.5      (c) 

Mixture 

47 

48 

49 

50 

7.6      (c) 

gree  of  acidity,  liowever,  is  in  many  cases  very  slight.  A 
very  faint  pink  solution  of  plienolphthalein  was  poured 
into  two  small  beakers,  so  that  the  tint  in  both  was  similar 


PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID      101 

Table  XIII — Continued 
H-IoN  Concentration   op  Nonmeningitic  Spinal  Fluid 


♦  Corked. 


i-H 

3  Hours 

4  Hours 

5  Hours 

12  Hours 

18  Hours 

24  Hours 

2  Days  and 
Over 

8  56   (a) 

8.14    (a) 

8.6      (a) 
9.08   (a) 
8  3      (a) 

7.89   (a) 

8.0 +  (b) 
8.6— (b) 

8.6— (b) 

8.0 +  (b) 

8.6 — (b) 

8.0      (b) 

8.6— (b) 

8.0      (C) 

8.0      (c) 

8.4      (c) 

8.2      (c) 

8.0      (c) 

8.1      (c) 

8.1      (C) 

8.1      (a) 

8.1      (C) 

8.1      (c) 

8.1      (c) 

8.1     (a) 
8.1      (C) 

8.1      (a) 
8.1     (c) 
7.7      (a)* 
7.7      (c) 
8.1      (c) 

8.1      (c) 
8.1      (c) 

8.1      (c) 

8.2      (a) 

8.1      (a) 

8.2      (C) 

in  looking  down  at  them  as  they  stood  upon  a  porcelain 
slab.  A  little  of  the  fluid  was  tlien  added  to  one  beaker  and 
generally  the  pink  color  was  immediately  discharged.     I 


102 


CEREBROSPINAL  FLUID 


found  that  the  fluid  left  unstoppered  in  my  room,  where  gas 
is  constantly  burning,  rapidly  becomes  alkaline,  whereas 
similar  fluid  in  stoppered  bottles  retained  its  acidity,  and 
that  in  my  later  examinations  where  this  source  of  fallacy 
was  recognized  and  excluded,  the  results  tend  more  and 
more  to  be  uniformly  acid  with  phenolphthalein. " 

I  have  endeavored  to  find  the  factors  that  are  responsi- 
ble for  the  changes  taking  place  in  the  H-ion  concentration 
of  nonmeningitic  cerebrospinal  fluid.  I  found  that  when 
I  put  a  part  of  the  cerebrospinal  fluid  right  after  its  with- 
drawal from  the  body  into  a  desiccator  containing  twenty 
per  cent  sodium  hydrate,  and  allowed  it  to  remain  in  the 
desiccator  from  ten  to  thirty  minutes,  the  acidity  of  the 
fluid  was  greatly  decreased,  the  Ph  being  in  a  very  short 
time  7.7  to  7.9. 

Table   XIV 

Changes   in   H+   Concentration   on    Removal   of   CO2   by    Exposure   to   Alkali    in 

Desiccator 


Ph 

case 

FLUID      DRAWN 

im- 
medi- 
ately 

exposed  to 

ALKALI 

exposed      to 

AIR 

examined 

Ph. 

190 

6:55  p.  m. 

7.4 

12  minutes 

7:07  p.  ni. 

7.7-7.8 

190 

6:55  p.  m. 

7.4 

20  minutes 

7:15  p.  m. 

7.8 

190 

6:55  p.  m. 

7.  J 

20  minutes 

7     minutes     after 

20   minutes 

exposure  to 

alkali 

7:22  p.  m. 

7.8-7.9 

190 

6:55  p.  m. 

7.4 

27  minutes 

38   minutes  after 

27    minutes 

exposure    to 

alkali 

7:55  p.  m. 

7.8-9 

190 

6:55  p.  m. 

7.4 

20  minutes 

13   hours 

11:22  a.  m. 

8.1 

188 

7:03  p.  m. 

7.4 

10  minutes 

7:13  p.  m. 

7.7-7.8 

188 

7:03  p.  m. 

7.4 

30  minutes 

7:33  p.  m. 

7.8 

188 

7:03  p.  m. 

7.4 

30  minutes 

3    minutes 

7:36  p.  m. 

7.8 

186 

7:45  p.  m. 

7.4 

6  minutes 

7:51  p.m. 

7.6-7.7 

186 

7:45  p.  m. 

7.4 

25  minutes 

8:10  p.  m. 

7.9 

This  shows  that  the  removal  of  CO2  from  the  fluid 
causes  a  decrease  in  the  Pl-ion  concentration  of  the  fluid. 
To  make  certain,  however,  that  the  increase  in  the  Ph  of 
the  cerebrospinal  fluid  is  entirely  due  to  CO2,  I  performed 
the  following  experiment.  I  divided  a  fluid  into  two  por- 
tions: one  portion  I  corked  tightly  after  its  removal  from 
the  body,  and  coated  with  a  layer  of  paraffin,  and  the  other 
portion  I  left  in  a  nonsol  glass  tube.    The  two  portions  of 


PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID 


103 


the  fluid  were  examined  twenty-four  hours  later.  I  found 
that  the  fluid  which  had  been  corked  very  tightly  retained 
the  original  H-ion  concentration,  giving  a  Ph  of  7.4  to  7.6  in 
twenty-four  hours;  while  the  fluid  that  had  heen  left  in  a 
cotton  plugged  test  tube  gave  a  Ph  of  8.1  or  higher  in 
twenty-'four  hours,  which  is  the  ordinary  change  taking 
place  in  cerebrospinal  fluid.  This  shows  that  the  decrease 
in  the  H-ion  concentration  in  the  cotton-plugged  tube  was 
not  due  to  formation  of  ammonia  or  other  alkaline  sub- 
stance, but  to  the  loss  of  CO2  from  the  fluid  into  the  air. 
I  have  furthermore  showai  that  when  the  tube  containing 


Pfl 

83 
%.7 
«i 

10 

n 

7.7 
7b 
7.5 
7.4 

p5§ 

^ 

. 

^^ 

' 

-^ 

^ 

j--^ 

^ 

r 

-] 

v>°'l 

"' 

1 

c 

-f-^ 

' 

.^■'^ 

^ 

t.y^ 

^A 

__    J 

1 

rti.H 

y' 

_Cc 

se2< 



=*= 

^ 





1 

-^ 

"Z^- 

■—- 

__C, 

pi-y 

1        2       3       4       5       fe       7       8       9      10      II       12     13     14      15       1 
Hours                                                                                                                       1 

Fig.  21. — Change  :n  H+  concentration  of  nonmeningitic  fluids  on  standing  at  room 
temperature  under  various  conditions.  Case  169.  Plugged  with  cotton.  Case  190.  Im- 
mediately after  withdrawal,  exijosed  to  CQo  free  air  in  desiccator  (dotted  line)  and  later 
left  with  cotton  plug.  Case  210b.  Plugged  with  cotton;  Case  210c,  the  same  fluid  as  b, 
but  corked  with  a  cork — a  few  bubbles  at  the  top.  Case  204.  Six.  c.c.  tube,  half  filled, 
and  tightly  corked;  cotton  plugged  fluid  was  same  as  Case  210b  (8.1).  Case  213.  Almost 
perfectly  sealed  with  cork,  without  any  air  bubble  above  the  fluid. 

fluid  is  corked  tightly,  but  some  space  is  left  between  the 
fluid  and  the  cork,  there  will  be  some  change  in  the  H-ion 
concentration  of  the  fluid,  the  H-ion  decreasing  slightly 
although  not  nearly  as  much  as  the  fluid  standing  in  the 
cotton-plugged  tul)e  (Table  XV)  (Fig.  21).  I  have  also 
measured  the  total  carbonates  in  fresh  and  old  fluid  and 
found  it  to  run  parallel  with  the  H-ion  concentration  as 


104 


CEREBROSPIXAL  FLUID 


Table  XV 
H  +    C0NCENTR.A.T10N   OF   Fluids  Standing  in  Corked  Tubes 


NUM- 
BER 

AGE 

DIAGNOSIS 

DATE    DRAWN 

DATE 
EXAMINED 

INTERVAL 

STOPPERED 
WITH 

Ph 

Mixture 
210a 

27 
38 

Alcoholic 
Alcoholic 

p.m. 
6/25/17  -  7:15 
6/25/17  -  7:20 

p.m. 
6/25/17  -  7:15 
6/25/17  -  7:20 

Immediately 
Immediately 

7.4 

7.4 

210b 

27 
38 

Alcoholic 
Alcoholic 

6/  5/17  -  7:15 
6/25/17  -  7:20 

a.m. 
6/26/17  -  8:00 

13  hours 

Cotton 

8.1 

210c 

27 
38 

Alcoholic 
Alcoholic 

6/25/17  -  7:15 
6/25/17  -  7:20 

6/26/17  -  8:00 

12  hours 

Paraffined  cork 
(few  bubbles 
below  cork) 

7.5-7.6 

211a 

43 

46 

Alcoholic 
Alcoholic 

6/25/17  -  7:28 
6/25/17  -  7:37 

6/25/17 
6/25/17 

Immediately 
Immediately 

7.5 

211b 

43 

46 

Alcoholic 
Alcoholic 

6/25/17  -  7:28 
6/25/17  -  7:37 

6/26/17  -  8:10 

12}^  hours 

Cotton 

8.1 

211c 

43 
46 

Alcoholic 
Alcoholic 

6/25/17  -  7:28 
6/25/17  -  7:37 

6/26/17  -  8:10 

12  M  hours 

Paraffined  cork 

7.5-7.6 

211d 

43 
46 

Alcoholic 
Alcoholic 

6/25/17  -  7:28 
6/25/17  -  7:37 

6/26/17  -11:17 

15J^  hours 

Paraffined  cork 
replaced  after 
3  c.c.  removed 
for   exam,    at 
8:10,    leaving 
3  c.c.  space  in 
6  c.c.  tube. 

7.6 

212 

55 

Alcoholic 

6/25/17  -  7:48 

6/25/17  -  7:52 

4  minutes 

7.4 

b 

55 

Alcoholic 

6/25/17  -  7:48 

6/26/17  -11:05 

15  hours 

Paraffined  cork 

7.5-7.6 

c 

56 

Alcoholic 

6/25/17  -  7:48 

6/26/17  -11:30 

15  hours 

Cotton 

8.2 

d 

55 

Alcoholic 

6/25/17  -  7:48 

p.m. 
6/28/17  -12:30 

Cotton 

7.9 

213 

39 

Alcoholic 

6/25/17  -  8:00 

6/25/17  -  8:02 

2  minutes 

7.5 

b 

39 

Alcoholic 

6/25/17  -  8:00 

6/26/17  -11:25 

15^  hours 

Paraffined  cork 

7.5-7.6 

218 

lyr. 

Pneumonia 

6/26/17  -  1:30 

6/26/17  -  1:30 

Immediately 

7.5-7.6 

b 

lyr. 

Pneumonia 

6/26/17  -  1:30 

6/28/17  -12:30 

47  hours 

Paraffined  cork 

7.5-7.6 

c 

lyr. 

Pneumonia 

6/26/17  -  1:30 

6/28/17  -12:30 

47  hours 

Cotton 

8.2 

204 

46 

42 
38 

Pulmonary 

tuberculosis 

Alcoholic 

General 

paresis 

6/18/17  -  7:15 

6/18/17  -  7:20 
6/18/17  -  7:30 

6/18/17  -  7:30 

15  minutes 

10  minute  1 
Immediately 

7.4 

b 

38 

General 
paresis 

6/18/17  -  7:30 

6/19/17  -  7':36 

12  hours 

Cotton 

8.1 

c 

38 

General 
paresis 

6/18/17  -  7:30 

6/19/17  -  7:30 

12  hours 

Paraffin;  left  3 
c.c.     space 
above  volume 
of  liquid. 

7.6-7.7 

205 

29 
34 
36 

Alcoholic 
Alcoholic 
Alcoholic 

6/18/17  -  7:40 
6/18/17  -  7:45 
6/18/17  -  7:53 

p.m. 
6/18/17  -  7:53 

11  minutes 

8  minutes 

Immediately 

7.4 

b 

36 

Alcoholic 

6/18/17  -  7:53 

a.m. 
6/19/17  -  7:55 

12  hours 

Cotton 

8,1 

c 

36 

Alcoholic 

6/19/17  -  7:53 

6/19/17  -  7:55 

12  hours 

Paraffined;  1  c.c. 
of    space  left 
on  top  of  fluid 

7.5-7.6 

PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID     105 

shown  in  Table  IX.  To  show  further  that  ammonia,  even 
if  absorbed  from  the  air,  is  a  negligible  factor,  I  made  the 
following  experiment:  A  fluid  ^vas  divided  into  two  por- 
tions, one  of  which  was  exposed  to  ammonia-free  air  in  a 
desiccator,  and  the  other  left  at  the  ordinary  laboratory 
temperature.  After  thirty  minutes  I  examined  the  two 
fluids  for  their  H-ion  concentration  and  found  it  to  be  the 
same  in  both  cases,  showing  that  the  usual  decrease  in  the 
H-ion  concentration  of  a  fluid  is  not  due  to  absorption  of 
ammonia  from  the  air. 

When  we  compare  H-ion  concentration  of  normal  cere- 
brospinal fluid  with  that  of  the  blood,  we  find  that  they  are 
both  the  same.  The  H-ion  concentration  of  the  blood  also 
ranges  between  a  Ph  of  7.4-7.6  immediately  after  being  re- 
moved from  the  body. 

Alkaline  Reserve 

I  determined  the  alkaline  reserve  on  the  amount  of  CO^. 
present  in  the  cerebrospinal  fluid  as  bicarbonate,  by  means 
of  the  Van  Slyke  alkaline  reserve  apparatus.  Table  XVI 
shows  the  alkaline  reserve  in  nonmeningitic  fluid: 

Table  XVI 
Alkaline  Reserve  of  Nonmeningitic  Cerebrospinal  Fluid 


NO. 

diagnosis 

alkaline    reserve 

1. 

Tabes 

5(5.5 

2. 

Poliomyelitis 

45.7 

3. 

Uremic  coma 

52.0 

4. 

Meningism 

47.5 

5. 

Chorea 

63.0 

6. 

Dementia  i>iei'ox 

58.75 

7. 

Psychosis 

55.72 

8. 

Cerebrospinal 

lues 

55.72 

9. 

Psychosis 

57.54 

The  above  shows  that  the  alkaline  reserve  of  nonmenin- 
gitic cerebrospinal  fluid  varies  between  45.7  and  63.0,  the 
average  being  l)etween  52  and  57%  of  COo  found  by  the 
cerebrospinal  fluid  at  0""  temperature,  at  760  barometric 
pressure,  which  is  about  the  same  as  the  alkaline  reserve  of 
blood. 


106 


CEREBROSPINAL  FLUID 


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PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID     107 

BIOCHEMICAL  PROPERTIES 

The  data  on  the  biochemical  properties  of  normal  cere- 
brospinal fluid  are  conflicting  in  nature.  Up  to  date  most 
of  the  biochemical  findings  reported  on  have  been  negative, 
but  it  is  possible  that  with  more  accurate  methods  posi- 
tive biochemical  properties  may  be  found. 

Amyloljrtic  Power 

Toison  and  Lenoble  found  that  the  cerebrospinal  fluid 
of  hydrocephalics  possesses  amylolytic  power.  Cavazzani 
reports  the  same.  Galletta,  however,  says  that  he  found 
this  to  be  true  in  only  two  out  of  eleven  cases  examined. 
Mestrezat  found  no  amylolytic  power  in  the  normal  cere- 
brospinal fluid  or  very  slight  traces  of  it. 

Proteolytic  Power 

Link  and  Pollack  report  finding  a  peptolytic  enzyme  in 
normal  cerebrospinal  fluid.  In  three  cases  of  hydroceph- 
alus and  one  case  of  spina  bifida  examined  for  the  presence 
of  pepsin  or  trypsin  Halliburton  found  no  trace  of  either. 
Miller  found  no  proteolytic  enzyme  or  antienzyme  in  nor- 
mal cerebrospinal  fluid. 

Galletta  found  a  fat-splitting  enzyme  in  three  of  seven 
cases.     Clerc  found  none. 

Glycol3^ic  Ferment 

Cavazzani  found  glycolytic  ferment  in  the  cerebrospi- 
nal fluid.  However,  neither  Panzar,  LeAvandowsky,  nor 
Mott  could  find  the  presence  of  any  glycolytic  ferment. 

Fibrin  Ferment 
Normal  fluid  contains  no  fibrin  ferment. 

Alexin 
Normal  fluid  contains  no  alexin. 


108  CEREBROSPIISrAL  FLUID 

Hemolysin 

Normally  no  hemolysin  is  found  in  the  fluid. 

Toxicity 

Normal  fluid  is  not  toxic,  compared  to  pathologic  fluid 
which  is  toxic. 

Bactericidal  Action 

The  question  as  to  whether  normal  fluid  has  a  bacteri- 
cidal action  has  not  yet  been  settled. 

CYTOLOGY 

The  study  of  the  cell  content  and  of  the  cell  elements  of 
the  cerebrospinal  fluid  was  inaugurated  in  France  by  Rav- 
ant,  Sicard,  Nagoette  and  Widal  in  1901,  and  has  since  been 
recognized  as  a  very  important  phase  of  the  study  of  the 
cerebrospinal  fluid. 

The  exact  number  of  cells  in  normal  cerebrospinal  fluid 
is  a  matter  on  which  authorities  who  have  worked  with  the 
fluid  do  not  agree.  Fuchs  and  Rosenthal  found  0  to  2  cells 
per  c.mm.  in  normal  fluid,  Rehm  found  1  to  5  and  even  6  to 
9,  and  Gennerich  found  8  cells  in  the  fluid  of  one  healthy 
person.  There  are  others  who  give  the  number  as  5  to  20 
per  c.mm.  The  reason  for  the  wide  discrepancy  is  the  fact 
that  different  investigators  have  employed  different  meth- 
ods in  determining  the  number  of  cells.  There  are  some 
who  count  the  cells  in  the  centrifuged  fluid,  using  a  certain 
amount  of  fluid  in  a  graduated  centrifuge  tube  and  taking 
one  drop  of  the  sediment  on  a  slide  (the  so-called  French 
method),  and  others  who  count  the  cells  in  counting  cham- 
bers. It  is  easy  to  see  how  these  two  methods  will  give  en- 
tirely different  results,  the  difference  being  at  times  as 
high  as  50  or  60  per  cent.  Even  those  who  count  the  cells 
in  a  counting  chamber,  get  variations  in  their  results  due 
to  the  type  of  chamber  they  use.     The  Fuchs-Rosenthal 


PROPERTIES  or  NORMAL  CEREBROSPINAL  FLUID     109 

chamber,  for  instance,  gives  a  smaller  percentage  of  error 
tlian  the  ordinary  leucocyte  counter.  The  greatest  source 
of  errors  responsible  for  the  discrepancy  of  findings  by 
various  authors  however,  is  the  admixture  of  blood  in  the 
cerebrospinal  fluid,  for  no  matter  how  clear  the  fluid  may 
look  there  may  be  some  blood  cells  obtained  by  the  passage 
of  the  needle  through  the  tissue,  which  would  in  turn  result 
in  enormous  errors,  when  figured  out  as  their  number  per 
c.mm.  In  addition  to  the  above  factors,  the  amount  of 
cerebrospinal  fluid  used  for  counting  and  the  use  of  a  stain 
may  account  for  the  difference  in  tlie  reports  of  the  various 
authors. 

I  found  the  number  of  cells  in  normal  fluid  to  be  between 
4  and  6  per  c.mm.  I  have,  therefore,  adopted  this  number 
as  an  arbitrary  standard,  anything  above  6  cells  per  c.mm. 
being  suspicious,  and  anything  above  10  cells  per  c.mm.  be- 
ing indicative  of  some  pathologic  condition  of  the  central 
nervous  system.  I,  of  course,  make  certain  that  the  cere- 
brospinal fluid  contains  no  blood  to  begin  with. 

Fischer  claims  that  the  result  obtained  in  the  cell  count 
of  fluid  obtained  by  lumbar  puncture  is  not  indicative  of 
the  cell  count  in  the  cerebrospinal  fluid  contained  in 
the  ventricle  of  the  brain.  This,  however,  has  been 
found  by  Nonne  not  to  be  true.  The  cell  content  in  the  fluid 
of  the  lumbar  region,  and  that  of  the  ventricle  are  found 
to  run  parallel  to  each  other.  I  have  found  that  the 
cell  content  in  the  different  portions  of  the  cerebro- 
spinal fluid  does  differ,  the  first  tube  containing  more  cells 
than  the  su})sequent  fluid.  I  believe  that  this  may  be  due 
to  a  contamination  of  blood  cells  in  the  first  portion  of  the 
fluid.  In  this  connection,  it  is  interesting  to  point  out  that 
one  author  advises  shaking  the  patient  from  side  to  side 
before  doing  a  liiml)ar  puncture,  in  order  to  stir  up  the 
cells  and  distribute  them  evenly  which,  of  course,  is  very 
absurd. 


110  CEREBROSPINAL  FLUID 

Type  of  Cell 

Normally,  no  red  blood  cells  are  found  in  the  fluid,  the 
cells  in  the  fluid  always  being  leucocytes.  The  normal 
type  of  leucocyte  in  cerebrospinal  fluid  is  the  small 
lymphocyte,  which  is  the  size  of  a  red  blood  cell  or  slightly 
smaller  or  larger  than  the  red  blood  cell.  The  nucleus  of 
the  lymphocytes  of  normal  cerebrospinal  fluid  is  round  or 
slightly  oval.  It  is  seldom  irregular.  The  nucleus  fills 
up  the  largest  part  of  the  cell  leaving  a  very  small  cell 
body.  No  granules  can  be  detected  in  the  cells,  as  a  rule. 
The  nucleus  stains  intensively  with  methyl-violet,  while 
the  cell  body  does  not. 

Large  lymphocytes  do  occur  in  normal  fluid  but  not  very 
frequently.  It  lias  been  observed  that  there  very  seldom 
exists  a  combination  of  large  and  small  lymphocytes  in 
the  same  specimen  of  fluid  that  gives  no  other  pathologic 
findings.  Large  IjTiiphocytes,  however,  always  should  make 
one  think  of  some  diseased  condition  of  the  central  nervous 
system. 

The  origin  of  the  cells  in  the  cerebrospinal  fluid  is  not 
fully  determined.  The  cells  in  normal  fluid  would  seem  to 
be  of  hematogenous  origin  as  they  are  small  lymphocytes 
with  occasional  large  forms  which  are  also  found  in  the 
blood.  On  the  other  hand,  the  cell  forms  in  the  fluid  of 
pathologic  conditions  are  often  very  different  from  those 
in  the  blood  and  this  suggests  some  other  source  for  the 
cells.  The  fibroblasts,  for  instance,  would  point  to  a  his- 
togenic  origin  of  the  cells.  It  is  possible,  of  course,  that 
the  cells  do  originate  in  the  blood  and  during  their  trans- 
mission into  the  cerebrospinal  fluid  or  while  in  the  cerebro- 
spinal fluid  may  change  forms.  Szecsi  suggested  that  some 
cells  originate  in  the  blood,  wiiile  fibroblasts  and  other 
such  elements  have  a  histogenic  origin.  I  believe  that  un- 
der normal  conditions  the  cells  in  the  cerebrospinal  fluid 
originate  in  the  blood  and  have  the  same  characteristics  as 
the  cells  in  other  parts  of  the  body. 


PROPERTIES  OF  NORMAL  CEREBROSPINAL  FLUID     111 

Bibliography 

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CerobiospiiialHiissigkoit  sowie  iiber  die  Wasserstoffioiien-Konzeiitration, 
Bioclicni.  Ztsclir.,  1914,  Iviii,  1. 

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xiv,  6,  393. 
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Kindern,  Arch.  f.  Kinderh.,  1898,  xxiv,  161. 
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X,  111. 
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Rev.  de  Med.,  1916,  xxxv,  511. 
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Jour.  Biol.  Chem.,  1915,  xx,  511. 
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Arch.  Int.  Med.,  1917,  xix,  1085. 
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search and    'leaching,   Jour.   Am.    Chem.   Soc,   1913,   xxxv,   817. 
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Virchows  Arcli.,  1859,  xvi,  391. 
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112  CEREBROSPINAL  FLUID 

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physiol.  Chem.,  1902,  xxxv,  202, 


CHAPTER  V 

PATHOLOGIC  CEREBROSPINAL  FLUID 

Cerebrospinal  fluid  reacts  to  all  processes  that  affect  the 
central  nervous  system.  The  chang-es  taking  place  in  the 
fluid  under  pathologic  conditions  are  due  to  two  causes: 
systemic  and  meningitic.  The  systemic  changes  are  due  to 
metabolic  disturbances  in  the  body  such  as  nephritis  or 
diabetes.  The  meningitic  changes  are  due  to  affections  of 
the  meninges.  These  may  be  divided  into  (1)  simple  ir- 
ritation of  the  meninges  or  of  the  brain  tissue;  (2)  in- 
fection of  the  meninges.  Irritation  of  the  meninges 
may  be  produced  by  mechanical  disturbances  in  the  cra- 
nial cavity,  or  by  the  action  of  metabolic  or  infectious 
toxins.  The  latter  condition  is  termed  serous  meningitis 
by  some,  and  meningism  by  others,  the  latter  term  being 
used  to  describe  all  conditions  wherein  the  meninges  are 
irritated  by  some  toxic  substance  which  increases  the 
amount  and  pressure  of  the  cerebrospinal  fluid  without 
changing  the  chemical  composition  of  the  fluid  or  affect- 
ing its  sterility.  This  is  the  condition  that  often  exists  in 
pneumonia,  influenza,  and  otitis  media.  Simple  irritative 
changes  produce  only  physical  alterations  in  the  fluid  or  at 
most  only  slight  physicocliemical  changes.  Changes  pro- 
duced by  the  entrance  of  bacteria  into  the  fluid,  on  the  con- 
trary, take  on  a  varied  character  and  may  be  physical, 
chemical,  cytologic,  and  bacteriologic.  These  changes  may 
appear  singly  or  in  various  combinations  at  one  and  the 
same  time.  Some  authors  voice  the  opinion  that  the  irri- 
tative and  infectious  changes  differ  in  degree  only,  and 
not  in  character.  I  believe,  however,  that  although  there 
are  changes  common  to  both  conditions,  those  in  infections 

113 


114  CEREBROSPINAL  FLUID 

are  different  in  type  from  those  of  simple  irritation.  Fur- 
thermore, the  reaction  is  specific  for  each  type  of  infection. 

Just  how  bacteria  may  enter  the  cerebrospinal  fluid  is 
still  a  matter  of  controversy.  There  are  two  ways  in  which 
they  can  make  their  entrance:  one  is  through  the  circula- 
tion and  the  other  is  by  direct  continuity  from  the  nose  or 
from  the  ears.  For  a  long  time  it  was  thought  that  the 
attack  of  the  meninges  in  epidemic  meningitis  or  in  polio- 
myelitis was  by  way  of  the  lymphatics  of  the  nasal  mucous 
membrane,  the  bacteria  passing  through  the  cribriform 
plate  of  the  ethmoid  directly  into  the  meninges.  How- 
ever, the  fact  that  the  meningococcus  in  many  cases  may 
be  cultivated  directly  from  the  blood  in  the  early  stages  of 
meningitis,  and  that  arthritis  and  iridochoroiditis  often 
complicate  meningitis  would  make  one  believe  that  the 
meningeal  infection  is  most  frequently  hematogenous.  The 
recent  work  of  Austrian  on  experimental  meningitis  is  also 
suggestive  of  the  septicemic  nature  of  meningococcic  in- 
vasion. 

In  tuberculous  meningitis  the  infection  hardly  ever 
reaches  the  meninges  directly  from  the  nose.  It  is  usually 
part  of  a  general  miliary  tuberculosis  of  which  the  menin- 
gitis is  a  terminal  process.  From  the  work  of  Albrecht 
and  Ghon,  we  know  that  the  primary  process  of  tubercu- 
losis usually  takes  place  in  the  lung,  and  gives  rise  to  an 
enlargement  of  the  hilus  glands,  which  in  time  either  be- 
comes retrogressive  with  calcification,  or  goes  on  to  a  gen- 
eral miliary  tuberculosis.  According  to  this  explanation, 
what  happens  in  tuberculous  meningitis,  then,  is  first  a 
tuberculous  infection  in  the  lung  tissue  proper;  second,  an 
infection  of  the  hilus  glands;  and  third,  an  invasion  of  the 
meninges  by  way  of  the  blood.  It  takes  some  time  before 
the  protective  wall  of  the  meninges  is  broken  through  by 
the  tubercle  bacilli,  but  they  finally  break  through  and  in- 
fect the  meninges.    That  tuberculous  meningitis  is  a  part  of 


PATHOLOGIC    CEREBROSPINAL   FLUID  115 

a  miliary  tuberculosis  is  seen  on  autopsy,  miliary  tubercles 
being  found  in  the  lungs,  liver,  and  spleen  in  all  cases. 

The  pneumococci  act  much  like  the  tubercle  bacilli  and 
meningococci  in  their  relation  to  meningitis.  Not  every 
pneumonia,  it  is  true,  produces  a  pneumococcus  meningitis 
but  almost  every  pneumococcus  meningitis  is  the  result  of 
a  pneumococcus  septicemia.  Some  observers  claim  that 
they  have  found  pneumococci  in  the  cerebrospinal  fluid  in 
uncomplicated  pneumonia,  but  this  seems  very  unlikely. 
There  is  no  apparent  reason  why  pneumococci  in  the  fluid 
should  produce  meningitis  in  one  instance  and  not  in  an- 
other. It  is  probably  safe  to  assume  that  if  no  meningitis 
is  produced  there  are  no  bacteria  in  the  cerebrospinal  fluid. 
The  nervous  system  is  the  master  system  of  the  body,  and 
Nature  has  provided  it  with  protection  by  surrounding  it 
with  cerebrospinal  fluid  and  with  three  layers  of  meninges^ 
one  of  which,  the  dura,  is  especially  heavy  and  firm.  In 
addition,  Nature  also  protects  the  meninges  with  the  heavy 
walls  of  the  skull  and  spine  and  in  spite  of  the  fact  that 
the  nervous  system  is  a  delicate  system,  and  that  the  cere- 
brospinal fluid  is  not  microbicidal  it  is  not  easy  for  bacteria 
to  gain  access  to  either. 

In  certain  cases  the  meningococci  and  other  bacteria 
find  their  way  into  the  cerebrospinal  fluid  through  the  crib- 
riform plates  of  the  ethmoid.  The  nasal  mucous  membrane 
may  harbor  pneumococci  and  streptococci,  meningococci 
and  influenza  bacilli,  and  it  is  conceivable  that  when  the 
system  is  in  a  low  state  of  resistance,  the  bacteria  may  en- 
ter the  meninges  directly.  The  cerebrospinal  fluid  in  these 
cases,  instead  of  being  a  means  of  protection  for  the  cen- 
tral nervous  system,  serves  as  a  good  medium  for  the  dis- 
semination of  the  bacteria. 

Still  another  route  for  the  entrance  of  bacteria  into  the 
cerebrospinal  fluid  is  the  ear.  In  advanced  cases  of  otitis 
media  or  mastoiditis,  the  bacteria  may  enter  the  brain 
substance,  in  whicli  case  they  produce  a  brain  abscess  or 


116  CEREBROSPINAL  FLUID 

the  meninges,  in  which  case  they  produce  a  meningitis. 
This  happens  most  frequently  in  infections  with  the  pnen- 
mococcus,  and  with  the  streptococcus  hemolyticus. 

Less  frequently  bacteria  make  their  way  into  the  cere- 
brospinal fluid  through  wounds  of  the  skull  and  spine,  es- 
pecially through  fractures  of  the  skull. 

Whichever  way  the  bacteria  enter  the  cerebrospinal 
fluid,  once  there,  they  produce  changes  in  the  meninges  or 
brain  and  give  rise  to  many  alterations  in  the  fluid.  Some 
of  the  changes  are  common  to  all  pathologic  processes  in 
the  meninges  or  brain,  whereas  others  are  specific  to  cer- 
tain bacteria  or  toxic  substances. 

Increase  in  Amount  of  Fluid 

It  is  the  rule  that  whenever  there  is  irritation  in  some 
serous  cavity,  the  fluid  normally  present  is  increased  in 
amount.  This  is  true  of  the  pleural  cavity,  the  peritoneum, 
pericardium,  and  also  of  the  meninges.  Any  irritation  of 
the  meninges,  therefore,  increases  the  amount  of  cerebro- 
spinal fluid,  the  increase  in  some  cases  being  only  moder- 
ate, in  others  very  great.  Is  every  case  of  increased  cere- 
brospinal fluid  to  be  termed  a  serous  meningitis  as  Quincke 
proposed?  It  would  seem  less  confusing  to  use  E.  Dupre's 
term  of  meningism  for  all  cases  where  the  fluid  shows  only 
physical  changes  and  reserve  the  term  meningitis  for  all 
processes  producing  chemical,  cytologic  and  bacteriologic 
changes.  The  name,  however,  makes  little  difference.  The 
important  fact  is  that  there  are  two  classes  of  irritation 
of  the  meninges.  It  should  be  noted  that  the  more  acute 
the  irritation,  the  greater  the  amount  of  fluid  accumulating 
in  the  ventricle  and  in  the  subarachnoid  spaces. 

Pressure 

With  the  increase  in  the  amount  of  fluid  in  the  subarach- 
noid there  is  naturally  an  increase  in  the  pressure  of  the 
fluid,  so  that  we  very  seldom  have  a  pathologic  process  of 


PATHOLOGIC    CEREBROSPINAL   FLUID  117 

the  meninges  without  a  corresponding  increase  of  the  pres- 
sure of  the  fluid.  Here  also  the  character  of  the  process  and 
the  degree  of  its  acuteness  determine  the  increase  in  pres- 
sure. 

Foam 

I  found  that  all  pathologic  fluids  produce  a  foam  on  shak- 
ing. When  a  test  tube  is  filled  one-third  to  one-half  its 
size  with  fluid,  and  is  shaken  for  two  or  three  minutes,  a 
heavy  foam  one  to  two  inches  in  thickness  forms,  persist- 
ing for  half  an  hour  or  longer.  When  normal  fluid  is  shaken 
in  a  test  tube  only  a  thin  foam  forms,  disappearing  in  a 
few  minutes.  The  foam  is  present  in  all  pathologic  fluids, 
but  it  is  of  greater  size  and  duration  in  acute  infections  of 
the  meninges.  Recently  Zingher  described  the  formation 
of  a  heavy  foam  in  poliomyelitis  which  corroborates  my 
observations.  It  seems  but  natural  to  think  that  the  foam 
production  is  due  to  the  CO2  in  the  fluid.  Close  observa- 
tion, however,  does  not  bear  this  out.  I  found  repeatedly 
that  a  foam  formed  just  as  readily  in  fluid  in  which  all  the 
CO2  had  been  driven  ofi^,  if  the  fluid  was  pathologic.  The 
foam,  therefore,  is  best  explained  by  the  increased  amount 
of  protein  in  the  fluid. 

CeUs 

Any  infection  of  the  meninges  gives  rise  to  an  increased 
number  of  cells  in  the  cerebrospinal  fluid.  The  cells  in 
disease  are  derived  from  the  congested  blood  vessels  of 
the  meninges,  the  number  of  the  cells  varying  with  the 
causative  organism  and  with  the  acuteness  of  the  process. 
The  character  of  the  cells  also  differs  with  the  type  of  the 
inflammation.  In  acute  inflammations  the  polynuclear  cells 
prevail  and  in  subacute  or  in  chronic  inflammations  the 
lymphocytes  are  the  rule.  In  general  paresis,  according 
to  Alzheimer,  plasma  cells  predominate. 

Does  an  increase  in  the  cells  of  the  cerebrospinal  fluid 
mean  a  corresponding  increase  in  the  white  cells  of  the 


118  CEREBROSPINAL  FLUID 

blood?  This  interesting  question  has  been  studied  by 
many  authors  who  found  that  although  the  leucocytes  in 
the  blood  are  usually  increased  in  meningitis,  the  leuco- 
cytes in  the  blood  and  those  in  the  fluid  do  not  necessarily 
run  parallel.  There  are  cases  of  meningitis  in  which  sev- 
eral thousand  cells  per  c.mm.  have  been  found  in  the  cere- 
brospinal fluid,  but  only  six  to  eight  thousand  leucocytes 
per  cubic  millimeter  in  the  blood.  There  are  other  cases  on 
the  contrary  where  there  is  a  high  leucocytosis  of  the  blood 
and  only  a  slight  increase  in  the  cells  of  the  cerebrospinal 
fluid. 

In  addition  to  these  changes  common  to  all  pathologic 
fluids,  there  are  changes  peculiar  to  special  types  of  dis- 
ease. The  changes  are  manifold,  physical,  chemical,  phys- 
icochemical,  and  bacteriologic.  I  shall  discuss  here  the 
mechanism  of  the  various  changes  and  leave  the  descrip- 
tion of  the  methods  for  the  next  chapter. 

Pellicle 

In  addition  to  the  physical  changes  which  make  their 
appearance  in  the  cerebrospinal  fluid  under  all  pathologic 
conditions  of  the  meninges,  such  as  an  increase  in  the 
amount,  in  the  pressure,  and  the  foam  of  the  fluid,  there 
is  one  change  which  takes  place  in  the  cerebrospinal  fluid 
that  is  fairly  characteristic  for  various  diseases.  This  is 
the  formation  of  a  pellicle. 

In  most  acute  diseases  of  the  meninges  a  pellicle  or  a 
net  of  fibrin  and  blood  cells  forms  in  the  fluid  on  standing. 
The  time  it  takes  a  pellicle  to  form  varies  with  the  charac- 
ter of  the  disease.  In  suppurative  meningitis,  the  pellicle 
forms  in  a  very  short  time.  In  tuberculous  meningitis,  it 
takes  from  twelve  to  twenty-four  hours  for  the  pellicle  to 
form,  although  I  have  seen  it  form  in  as  short  a  time  as  one 
hour.  Some  authors  have  described  a  pellicle  formation  in 
poliomyelitis  and  in  lues  of  the  central  nervous  system.  I 
have  observed  a  pellicle  in  poliomyelitis  only  very  rarely.  I 


PATHOLOGIC    CEREBROSPINAL   FLUID 


119 


have,  however,  observed  a  certain  sediment  in  some  cases 
of  tabes  dorsalis  and  in  certain  cases  of  cerebrospinal  lues. 
The  sediment  formed  was  flocculent  in  type,  resembling  the 
floccnli  formed  by  the  Noguchi  test,  or  after  the  addition  of 
sodium  hydrate  to  the  fluid  of  tuberculous  meningitis. 

The  pellicle  consists  of  a  separation  of  the  heavier  ele- 
ments of  the  cerebrospinal  fluid,  so  that  microscopically 


Fig.   22. — Photomicrograph  of   stained  pellicle   from  cerebrospinal  fluid   of  a  pneumococcus 

meningitis. 


one  can  see  in  the  pellicle  many  leucocytes  on  a  fibrinous 
background.     (Fig.  22.) 

The  formation  of  a  pellicle  depends  on  three  factors:  (1) 
fibrin;  (2)  fibrin  ferment;  (3)  blood  cells.  Of  these  three 
factors  the  most  important  is  the  fibrin,  although  the  other 
two  also  play  an  important  role.  The  addition  of  blood 
serum  to  the  cerebrospinal  fluid  accelerates  the  formation 
of  a  pellicle,  but  it  is  generally  inadvisable  to  add  blood 
serum,  as  it  interferes  mth  chemical  tests. 

The  pellicle  not  only  indicates  the  existence  of  a  patho- 
logic condition,  but  also,  I  believe,  serves  to  show  the  phys- 


120 


CEREBROSPINAL  FLUID 


ical  changes  produced  in  various  fluids.  Fig.  23  illus- 
trates the  various  forms  of  pellicle  in  various  diseases  as 
observed  early  before  autolysis  takes  place. 

Crystallization 

Another  physical  phenomenon  which  takes  place  in  cere- 
brospinal fluid  on  standing,  is  the  formation  of  crystals, 


B.  C.  D.  E.  F. 

Fig.   23. — Pellicle    formation    in    meningitis. 


G. 


A.  Normal.  B.  Meningococcus  meningfitis,  fairly  early.  C.  Meningococcus  menin- 
gitis, advanced  (sulphur-like  granules).  D.  Meningococcus  meningitis,  late  in  disease. 
E.  Meningococcus  meningitis,  severe,  on  road  to  recovery.  F.  Pneumococcus  menin- 
gitis,   fatal.      G.      Pneumococcus    meningitis,    fatal.      H.      Tuberculous    meningitis. 

their  character  depending  on  the  character  of  the  disease. 
Various  authors  have  called  attention  to  the  crystals  found 
in  the  cerebrospinal  fluid.  Mott  speaks  of  cholin  crystals 
in  the  fluid  of  patients  suffering  from  disease  producing  a 
degeneration  of  the  nervous  tissue.     Thomson  describes 


PATHOLOGIC    CEREBROSPINAL   FLUID 


121 


Fig.   24. — Crystals   formed   in   test   tube   on   spontaneous  evaporation   of  cerebrospinal   fluid 
from  a  case  of  tuberculous  meningitis. 


Fig.  25. — Spontaneously  evaporated 
fluid  from  another  case  of  tuberculous 
meningitis. 


Fig.  26. — Spontaneously  evaporated 
cerebrospinal  fluid  from  a  case  of 
pneumococcus    meningitis. 


the  presence  of  elongated,  colorless,  transparent  crystals 
in  septic  meningitis.  He  suggests  that  the  acid  radical 
present  in  the  crystals  is  most  likely  phosphoric  acid.    I 


122 


CEREBROSPINAL  FLUID 


Fig.    27-A. — Crystals    from    an    evaporated    fluid    in    a    case    of    tuberculous    meningitis. 

(76  diameters.) 


^^ 


^ 

^ 


"-t 


^ 


/r.> 


o 


t. 


n 


Fig.    27-B. — Crystals   from   another   evaporated   fluid   of   a   case   of   tuberculous    meningitis. 

(76  diameters.) 


PATHOLOGIC    CEREBROSPINAL   FLUID 


123 


made  a  study  of  the  crystalization  process  in  a  great  num- 
ber of  pathologic  fluids  which  were  allowed  to  evaporate 
spontaneously  at  room  temperature,  and  found  that  after 
several  months  of  standing,  most  pathologic  fluids  showed 
the  presence  of  many  crystals  of  various  sizes  and  shapes 
different  from  those  formed  in  normal  fluids.  Figs.  24,  25, 
and  26  show  the  different  forms  of  crystals  present  in  dif- 
ferent conditions,  the  varieties  being  even  more  distinct  on 
microscopic  examination.     (Figs.  27  and  28.) 


*i5':^'^ 


,  \ 


(&  ^ 


^ 


1^^ 


Fig.    28. — Crystals    from    an    evaporated    Huul    ot    a    case    of    pneumococcus    tneningitis. 

(76   diameters.) 


Permanganate  or  Organic  Index 

Mayerhofer  was  able  to  show  by  means  of  the  Kubl  Thie- 
mich  permanganate  method  that  there  is  an  increase  in  the 
organic  substance  in  cerebrospinal  fluid  in  all  meningitides. 
This  increase,  he  found,  could  be  measured  by  the  amount 
of  permanganate  necessary  to  oxidize  the  organic  sub- 
stance. Mayerhofer 's  observations  led  him  to  the  follow- 
ing conclusions : 


124 


CEREBROSPINAL.  FLUID 


Table    XVIII 
Organic    Index  in  Cerebrospinal  Fluid  in  Various  Forms  of  Meningitis 


permanganate 

index 

NAME 

diagnosis 

TUBE  I 

TUBE  II 

TUBE  III 

TUBE  IV 

TUBE  V 

A.M. 

Tuberculous  meningitis 

3.0 

3.0 

A.M. 

Tuberculous  meningitis 
(Same  case  4  days  later.) 

2.9 
3.35 

2.6 

3.2 

4.55 

(15  c.c. 

between) 

J.  P. 

Tuberculous  meningitis 
(Examined  2  days  later) 

2.55 
2.95 

1.77 
1.55 

1.6 
1.75 

D.  H. 

Tuberculous  meningitis 
(Examined  3  days  later) 

3.1 
3.9 

1.8 

3.0 

2.7 

2.7 

M.H. 

Tuberculous  meningitis 

2.1 

1.8 

D.  K. 

Tuberculous  meningitis 

2.6 

2.2 

E.S. 

Epidemic  meningitis 

7.9 

E.  C. 

Epidemic  meningitis 

5.6 

D.  S. 

Epidemic  meningitis 

2.0 

0.  C. 

Epidemic  meningitis 
(12    hours    after    serum 
injection) 

9.2 
7.3 

9.3 

8.7 

M.E. 

Influenza  meningitis 

2.6 

E.  M. 

Pneumococcus  meningitis 
(Examined?  days  later) 

3.3 
4.6 

4.3 
4.3 

3.0 
4.6 

H.N. 

Pneumococcus  meningitis 

4.7 

4.7 

4.7 

(1)  That  tlie  reduction  index  of  normal  cerebrospinal 
fluid  is  low.  Different  portions  of  the  same  fluid  give 
either  the  same  reduction  index  or  a  different  one,  the 
tendency  being  toward  a  higher  index  in  each  subsequent 
portion. 

(2)  That  the  reduction  index  of  meningitis  is  higher 
than  that  of  normal  cerebrospinal  fluid  (2  and  up).     Un- 


PATHOLOGIC    CEREBROSPINAL   FLUID  125 

like  normal  fluid,  the  index  becomes  lower  with  each  sub- 
sequent portion  of  the  fluid. 

(3)  That  the  reduction  index  of  cerebrospinal  fluid  in 
epidemic  meningitis  drops  to  one-half  its  original  patho- 
logic rate  after  an  injection  of  meningococcic  serum. 

My  work  on  the  permanganate  index  gave  similar  re- 
sults. I  found  that  fluid  of  all  forms  of  meningitis  gives 
a  higher  organic  index  than  normal  fluid  and  that  the 
fluid  of  suppurative  meningitides  gives  a  higher  organic 
index  than  fluid  of  tuberculous  meningitis.  Table  XVIII 
gives  some  of  the  findings  with  the  permanganate  index  in 
fluid  of  various  diseases. 

Protein 

In  normal  cerebrospinal  fluid  the  protein  content  is  small 
and  consists  mainly  of  globulin.  In  pathologic  conditions 
there  is  both  an  increase  in  the  amount  of  the  protein  and 
a  change  in  its  character,  as  Table  XIX  of  Mestrezat  shows. 
(Figures  expressed  in  grams  per  liter). 

Table  XIX 

GLOBULIN        SERUM 
A^^UMIN  ^Q  GLOBULIN 


Tuberculous 

1    gm. 

15 

0    gm. 

15 

7/1 

meningitis 

1    gm. 

35 

0    gm. 

25 

5.5/1 

0    gm. 

80 

0    gm. 

40 

2/1 

Cerebrospinal 

1    gm. 

80 

0    gm. 

30 

6/1 

meningitis 

2    gm. 

50 

0    gm. 

31 

8/1 

Syndrome  of 

4    gm. 

90 

1    gm. 

30 

3/1 

massive  coagulation 

6    gm. 

50 

2    gm. 

20 

3/1 

Precipitation 

The  action  of  the  precipitants  on  cerebrospinal  fluid  in 
various  diseases  furnishes  another  evidence  of  the  varying 
character  of  the  protein  in  different  diseases.  Tashiro  and 
I  found  that  in  certain  pathologic  conditions  a  character- 


126 


CEREBEOSPIXAL  FLUID 


istic  ratio  may  be  obtained  between  the  precipitate  formed 
by  sulphosalicylic  acid  and  that  formed  by  mercuric 
chloride.  AVe  based  our  comparison  on  the  assumption 
that  different  processes  respond  differently  to  alkaloidal 


i-f 

ill 

J 

4  -v^^H 

/.  2.  3-  4-  5-  6. 

Fig.   29. — Photograph  showing  the  typical  ratio  of  precipitates  by  the  two  precipitants. 

1.  1   c.c.   of  nonmeningitic  fluid  plus   1    c.c.   of  3  per  cent  sulphosalicylic   acid. 

2.  1  c.c.   of  nonmeningitic  fluid  plus   1   c.c.  of   1   per  cent  HgClo. 

3.  1   c.c.  of  fluid  from  epidemic  meningitis  plus   1   c.c.    of  sulphosalicylic  acid. 

4.  1    c.c.    of   fluid    from    epidemic    meningitis   plus    1    c.c.    of    IlgClo. 

5.  1   c.c.   of  fluid   from   tuberculous  meningitis   plus   1    c.c.   of  sulphosalicylic   acid. 

6.  1   c.c.   of  fluid  from  tuberculous  meningitis  plus   1   c.c.   of  HgClo. 


precipitants,  such  as  sulphosalicylic  acid  and  metallic  pre- 
cipitants, such  as  mercuric  chloride  (Tables  XX,  XXI, 
andXXII,  Fig.  29). 


PATHOLOGIC    CEREBROSPINAL   FLUID 


127 


Table  XX 

Comparison  of  Amount  of  Sediment  from  the  Metallic   and  Alkaloidal 
Precipitation  with  Nonmeningitic  Fluids 


measurements    of   the    depth   of 
sediment  in  mm.  after  24  hours 


number 

DIAGNOSIS 

1 

Psychosis 

2 

Tic 

3 

General  paresis 

4 

Delirium    tremens 

5 

General  paresis 

6 

Psychosis 

7 

General  paresis 

8 

General  paresis 

9 

Psychosis 

10 

Psychosis 

11 

Psychosis 

12 

Meningism 

13 

Dementia  precox 

14 

Alcoholic 

15 

Psychosis 

16 

Psychosis 

17 

Psychosis 

18 

Psychosis 

19 

Meningism 

HgCU 


Sulphosalicylic  Acid 


3 

4 

43^ 

3 

3^ 

3 

3^ 

3 

4 

4 

4 

3 

3 

3 

3 

4 

3 

3 


Table  XXI 

Amount  of  Sediment  from  the  Metallic  and  Alkaloidal  Precipitation 
from  Fluid  of  Tuberculous  Meningitis 


measurements   of   the    depth    of 
sediment  in  mm.  after  24  hours 


number 

HgC 

1 

10 

2 

15 

3 

10 

4 

11 

5 

6 

6 

7 

7 

9 

8 

IS 

9 

11 

10 

10 

11 

6 

12 

10 

13 

20 

Sulphosalicylic  Acid 


4 

4 

5 
3 
3 
6 
5 
7 
4 
S 
4 
5 


128 


CEREBROSPINAL  ELUID 


Table  XXII 

Measurement  of  Sediment  from  Metallic  and  Alkaloidal  Precipitation 
FROM  Fluid  in  Epidemic  Meningitis  Before  Serum  was  Given 


measurements    of   the    depth    of 
sediment  in  mm.  after  24  hours 


HgCls 


Sulphosalicylic  Acid 


7 
20 
10 
20 


These  findings  which  can  be  utilized  for  diagnostic  pur- 
poses speak  in  favor  of  my  contention  that  there  are  spe- 
cific changes  produced  by  various  disease  processes  which 
manifest  themselves  both  chemically  and  physicochemically. 
Although  the  fluid  in  eases  of  tuberculous  meningitis 
contains  less  organic  substances  than  the  fluid  of  epidemic 
meningitis  as  the  table  on  organic  index  shows,  still  the 
mercuric  chloride  solution  produces  a  heavier  sediment  in 
tuberculous  meningitis  than  it  does  in  epidemic  meningitis. 
Table  XXIII  shows  further  that  the  precipitants  in  ques- 
tion do  not  bear  any  quantitative  relation  to  the  amount  of 
protein  present  in  the  cerebrospinal  fluid.    In  determining 


Table  XXIII 


MERCU- 

SULPHO- 

RIC 

SALICYL 

APPEAK- 

AMOUNT 

CHLORIDE 

IC  ACID 

CASE 

DIAGNOSIS 

ANC?: 

OF 

SEDI- 

SEDI- 

OF   FLUID 

PrvOTEIN 

MENT 

After  24 
hours 

MENT 

After  24 
hours 

230 

Tuberculous 

Clear 

0.1% 

20  mm. 

5  mm. 

231 

meningitis 
Tuberculous 

Clear 

0.1% 

IS  mm. 

7  mm. 

232 

meningitis 
Tuberculous 

Clear 

0.9% 

14  mm. 

6  mm. 

233 
234 

meningitis 
Epidemic 

meningitis 
Epidemic 

meningitis 

Turbid 
Turbid 

0.3% 
0.25% 

5  mm. 
7  mm. 

20  mm. 

20  mm. 

PATHOLOGIC    CEREBROSPINAL   FLUID  129 

the  amount  of  protein  present  in  the  fluid  I  used  the  method 
of  Esbach,  except  that  I  used  half  the  proportions  ad- 
vised for  urine.  I  also  added  to  the  cerebrospinal  fluid 
and  the  reagent,  one  drop  of  a  10  per  cent  solution  of  acetic 
acid.  I  put  the  entire  solution  into  a  small  centrifuge  tube 
which  I  allowed  to  stand  for  24  hours  undisturbed.  I  did 
not,  however,  centrifuge  the  mixture. 

Sugar 

The  study  of  sugar  in  the  cerebrospinal  fluid  in  its  rela- 
tion to  certain  diseases  of  the  meninges,  has  occupied  an 
important  place  in  the  literature.  Kopetzky  found  an  en- 
tire absence  of  sugar  in  all  cases  of  meningitis.  His  method 
of  detennination  was  qualitative,  however,  not  quanti- 
tative. Connall  reported  an  absence  of  sugar  in  all  acute 
infections  of  the  meninges.  Schloss  observed  an  absence 
of  sugar  in  some  cases  of  tuberculous  meningitis  and  a 
small  amount  in  others.  Hopkins  found  a  smaller  amount 
of  sugar  in  the  fluid  of  syphilitics  than  in  any  other  condi- 
tion except  meningitis.  My  own  work  on  sugar  in  path- 
ologic cerebrospinal  fluids  with  Strouse  gave  no  alteration 
in  the  fluid  of  lues  which  we  found  to  contain  a  normal 
amount  of  sugar  and  gave  an  increase  of  sugar  in  diabetes, 
and  either  an  entire  absence  of  sugar  in  various  forms  of 
meningitis,  or  its  presence  in  small  or  normal  amount.  Ta- 
bles XXIV,  XXV  and  XXVI  give  sonie  of  our  results. 

Table  XXIV 
Sugar  Conte^nt  in  the  Cerebrospinal  Fluid  q^  Lues 


NAME 

WA8SERMANN  TEST 

sugar  CONTENT 

P.  N. 

Btroiigly  positive 

0.104% 

M.L. 

Strongly  positive 

0.104 

P.  G. 

Positive 

0.064 

M.L. 

Strongly  positive 

0.048 

J.J. 

Positive 

0.070 

J.L. 

Positive 

0.074 

E.M. 

Suspicious 

0.080 

130  CEREBROSPINAL  FLUID 

Table  XXV 
Sugar  Content  in  Cerebrospinal  Fluid  of  Diabetes 


NAME 

SUGAR   CONTENT 

Cerebrospinal  Fluid       Blood               Urine 

T.  G. 

0.076 

0.080                 0.42 

D.  K. 

0.38 

M.  B. 

0.28 

0.24 

Table  XXVI 

Sugar  Content 

IN  THE 

Cerebrospinal  Fluid  of  Meningitis 

name 

diagnosis 

SUGAR 

J.  p. 

Tuberculous   meningitis 

Absent 

E.L. 

Tuberculous   meningitis 

0.08% 

A.M. 

Tuberculous   meningitis 

Absent 

M.E. 

Tuberculous   meningitis 

0.038 

M.L. 

Tuberculous   meningitis 

0.032 

I.W. 

Tuberculous   meningitis 

0.024 

O.C. 

Meningococcus  meningitis 

Absent 

H.F. 

Meningococcus  meningitis 

0.024 

M.K. 

Meningococcus   meningitis 

0.028 

J.R. 

Meningococcus   meningitis 

Absent 

M.H. 

Meningococcus  meningitis 

Absent 

S.N. 

Pneumococcus    meningitis 

Absent 

E.S. 

Pneumococcus    meningitis 

Absent 

Among  the  other  chemical  constituents  that  undergo 
changes  in  certain  diseases,  are  urea,  phosphates,  cholin, 
and  cholesterol.  In  nephritis  and  uremia  the  urea  has 
been  found  to  be  3.7  per  cent  and  even  as  high  as  4.5 
per  cent,  compared  to  0.003  and  0.090  per  cent  in  normal 
fluid.  Some  workers  have  also  observed  an  increase  of 
urea  in  the  fluid  in  cases  of  arteriosclerosis  with  symp- 
toms pointing  to  an  involvement  of  the  central  nervous 
system.  Phosphates  were  found  by  Donath  to  be  increased 
in  conditions  of  rapid  nerve  degeneration,  such  as  pro- 
gressive paralysis,  tabes  dorsalis  and  tumor  of  the  brain. 
Mott  and  Halliburton  found  cholin  in  the  fluid  and  also 
sometimes  in  the  blood  in  cases  of  severe  nervous  lesions, 
especially  in  paresis.  Donath  found  cholin  in  the  fluid  of 
epileptics  and  paretics,  the  largest  amount  being  present 
in  the  latter.  Pighini  reported  the  presence  of  cholesterol 
in  cases  of  general  paralysis,  dementia  precox,  and  epi- 


PATHOLOGIC    CEREBROSPINAL   FLUID  131 

lepsy.  It  was  found  to  be  present  in  88  per  cent  of  general 
paralysis,  in  66  per  cent  of  epilepsy,  and  in  43  per  cent  of 
dementia  precox. 

The  chlorides  were  increased  in  the  cases  of  nephritis  I 
examined.  In  the  cases  of  meningitis  I  examined  the  chlo- 
rides differed  with  the  type  of  infection  as  seen  from  Ta- 
ble XXVII. 

Table  XXVII 
Chlorides  in  Meningitic  Fluid 


NO. 

diagnosis 

CHLORIDES     IN     GH. 
PER    100    C.C. 

1. 

Streptococcus  meningitis 

0.80 

2. 

Meningococcus  meningitis 

l)efore  serum 
Same    patient    after    serum 

0.70 
0.72 

3. 

Pneumococcus    meningitis 

0.60 

4. 

Tuberculous   meningitis 

0.50 

Lactic  acid  was  increased  in  the  cases  of  suppurative 
meningitis  I  examined.  It  usually  took  only  5  to  6  drops  of 
cerebrospinal  fluid  to  turn  5  c.c.  of  Uffelman's  reagent  to 
canary  yellow  instead  of  18  to  20  drops  required  for  non- 
meningitic  fluid.  Acetone  was  present  in  some  cases  aftei' 
the  fluid  had  been  standing  for  several  days.  In  a  case  of 
influenza  meningitis  there  was  a  deep  violet  ring  such  as 
occurs  in  urine  loaded  with  acetone.  On  a  number  of  fluids 
from  meningococcus  meningitis  the  nitroprusside  test  for 
acetone  gave  a  deep  green  ring. 

Turbidity 

By  using  one  c.c.  of  cerebrospinal  fluid  in  a  test  tube  one- 
third  inch  in  diameter,  and  adding  to  the  fluid  small  por- 
tions of  decinormal  sodium  hydrate  and  decinormal  sul- 
j)liuric  acid,  I  was  abk'  not  only  to  detect  the  presence 
of  a  pathologic  process,  but  also  to  get  a  clue  as  to  the  type 
of  the  disease.  Normal  cerebrospinal  fluid  shows  no  tur- 
bidity on  the  addition  of  either  sulphuric  acid  or  of  sodium 


132 


CEREBROSPINAL  FLUID 


hydrate.  The  fluid  of  tuberculous  meningitis,  however,  is 
not  affected  by  sulphuric  acid,  but  is  precipitated  by  a  very 
small  amount  of  sodium  hydrate.  The  fluid  of  suppurative 
meningitis,  which  is  turbid  to  begin  with,  is  cleared  up  by 
sodium  hydrate  and  is  not  affected  by  sulphuric  acid. 


PHYSICAL  CHEMISTRY 

Among  the  most  important  changes  that  make  their  ap- 
pearance in  pathologic  conditions  of  the  nervous  system 
are  those  of  a  physicochemical  character.  Although  not 
all  physicochemical  changes  are  of  diagnostic  value,  they 
are  all  of  significance  in  that  they  bring  out  specific 
changes  typical  of  special  diseases.  What  is  more,  further 
investigations  on  the  physicochemical  changes  taking 
place  in  pathologic  cerebrospinal  fluids  give  promise  of  an 
even  wider  range  of  information  that  can  be  applied  with 
equal  effectiveness  to  pathologic  conditions  of  other  body 
fluids,  such  as  blood  and  urine. 

Table  XXVIII  will  show  some  of  the  variations  found  in 
physicochemical  constants  in  various  pathologic  conditions 
of  the  cerebrospinal  fluid. 

Table  XXVIII 
Physicochemical   Findings   in   Various   Forms   of   Meningitis 


H-ION 

specific 

viscos- 

FREEZING 

conduc- 

concen- 
tration 

ALKALINE 

GRAVITY 

ity 

point 

tivity 

RESERVE 

Epidemic 

1.0075 

1.0434- 

-.55°  to 

.011629 

Immed. 

18-      38% 

meningitis 

1.0735 

-.57°C. 

7.3 
On  Stand- 
ing 

P„ 
Increases 

slowly 
or  may  be- 
come 

more  acid 

of  CO, 

bound 

by  the 

fluid 

Tuberculous 

1.00693- 

1.0693 

-.47° 

.013660 

7.4r- 

33-    58% 

meningitis 

1.00626 

7.6 

Increases 

to 

8.1   & 
higher 

of  CO, 

PATHOLOGIC    CEREBROSPINAL   FLUID 


133 


A  comparison  of  these  figures  with  those  given  for  nor- 
mal fluid  (Chapter  IV)  sliows  the  great  variation  between 
the  physicochemical  constants  of  pathologic  and  normal 
fluids.  Other  authors  have  reported  even  greater  differ- 
ences. Achard,  Loeper  and  Lanhry  found  the  freezing 
point  of  fluid  from  tuberculous  meningitis  to  be  -.44°,  and 
that  of  epidemic  meningitis  -.46°,  whereas  the  freezing 
point  of  normal  fluid  usually  varies  between  -.56°  and  -.58°. 


PROTEIN  CHARGES 

It  is  well  known  that  the  electrical  charge  of  a  protein 
depends  on  the  reaction  of  the  medium.  In  acid  solution, 
proteins  become  electropositive,  and  in  alkaline  solutions 
they  become  electronegative,  as  showai  in  Table  XXIX. 

Table  XXIX 
Showing  Cataphoresis  of  Proteins;  Figures  Taken  from  Michaelis 


SITBSTAXCES 

H+ 

MOVES  TO 

Casein 

Serum  Albumin 

4.9  X  10-5 

4.1  X  10-5 

1.3  X  10-5 

1.2  X   10-"  —  2.1 

X  10-5 
2.0   X   10-5—  1.9 

X  10-5 
1.1   X   10-5—  1.9 
X  10-5 

2.4  X  10-' 

1.2  X  10-' 

1.5  X  10-5 
1.2   X   10-5  —  3.5 

X  10-5 
3.9  X  10-5 

Cathode 

Stand  still 

Anode 

Cathode 

Oxyhemoglobin 

Stand  still 
Anode 

Cathode 

Gelatin 

Anode 
Anode 

Stand  still 
Cathode 

It  is  thus  seen  that  one  way  of  precipitating  protein  is 
to  let  it  combine  with  some  radicle  to  form  an  insoluble 
protein  salt.  From  the  standpoint  of  the  electrical  charge 
ol*  the  protein  such  a  protein  is  necessarily  either  a 
positive  protein  radicle  forming  a  protein  salt  with  nega- 


134 


CEREBROSPINAL  FLUID 


lively  charged  ions  (alkaloidal  precipitants),  such  as 
tungstic,  picric,  tannic  acid  and  the  like,  or  a  negatively 
charged  protein  combining  with  a  positively  charged  metal 
(metallic  precipitants)  such  as  Cu,  Ag,  Hg,  Zn,  and  Pb. 
If  these  protein  salts  are  sufficiently  insoluble,  a  precip- 
itate will  come  down. 

To  ascertain  whether  the  difference  in  the  acidity  of  the 
cerebrospinal  fluid  under  various  conditions  as  discussed 
below  is  great  enough  to  produce  different  electrical  states 
of  the  proteins  in  the  fluids,  I  have  made  a  series  of  observa- 


Fig.    30. — Apparatus    for    cataphoresis    of   proteins,    after   Michaelis. 

tions.     The  apparatus  used  was  the  one  recommended  by 
Michaelis.    (Fig.  30.) 

The  fluids  w^ere  placed  in  3,  care  being  taken  to  see  that 
there  was  no  bubble  inside  the  core  of  the  stopcocks.  Tubes 
2  and  4  were  filled  with  3  per  cent  sulphosalicylic  acid, 
and  the  upper  portions  (1  and  5),  with  distilled  water.  To 
one  electrode  was  added  CuClz  and  to  the  other  NaCl;  a 
silver  electrode  was  put  in  the  anode  and  a  copper  electrode 
in  the  cathode.  The  poles  were  connected  to  a  light  circuit 
with  110  volt  constant  current,  with  an  ordinary  lamp  in 
the  circuit  as  resistance.    The  object  was  to  determine  the 


PATHOLOGIC    CEREBROSPINAL   FLUID 


135 


pole  to  which  the  protein  would  move.  The  migration  of 
the  protein  from  the  cerebrospinal  fluid  was  detected  by 
the  formation  of  a  precipitate  with  sulpho salicylic  acid 
in  the  arm.  This  method,  of  course,  is  necessarily  crude. 
For  an  accurate  test  it  would  be  necessary  that  the  H-ion 
concentration,  the  osmotic  pressure  of  the  precipitants  and 
of  cerebrospinal  fluid  be  the  same  for  each  experiment — a 
procedure  almost  impossible  on  account  of  the  variation  in 
the  fluid.  Furthermore,  under  these  conditions,  positively 
charged  protein  has  a  better  chance  of  forming  precipi- 
tates at  the  cathode,  while  negatively  charged  protein,  which 
moves  to  the  anode,  must  change  its  charge  at  the  anode 
in  order  to  combine  with  sulphosalicylic  acid.  In  other 
words,  the  amount  of  negatively  charged  protein  to  be  pre- 
cipitated at  the  anode  depends  not  only  on  the  amount  of 
protein  that  moves  to  the  anode,  but  also  on  the  strength 
of  the  acidity  of  the  precipitating  agent  at  the  anode.    Al- 


Table  XXX 
Results  of  Cataphohesis  on  Fluid  from  Cases  of  Tuberculous  Meningitis 


CATAPHOHESIS 

NUMBER 

TIME    AFTER 
WITHDRAWAL 

Cathode 

Anode 

1 

2  hours 

i 

1 

1 

2  days 

I 

1 

1 

2  days 

I 

2 

2  hours 

1 

2 

3  hours 

1 

3 

1  day 

1 

4 

3  hours 

I 

5 

24  hours 

1 

i  Indicates  heavy  precipitate. 
I  Slight  precipitate. 


136 


CEREBROSPINAL  FLUID 


Table  XXXI 
Results  of  Cataphoresis  on  Fluids  from  Epidemic  Meningitis 


CATAPHORESIS 

NUMBER 

INTERVAL 

remarks 

Cathode 

Anode 

1 

1  day 

M 

1 

1  day 

I 

2 

20  hours 

I 

2 

3  days 

i 

3 

3  days 

i 

3 

2  days 

i 

1 

Fluid  bloody 

3 

4 
5 

3  hours 

8  hours 
3  hours 

1 

w 

i 
i 

i 

1 
1 

fUnusually    alkaline    fluid; 
cases    brought    in    from 
another     hospital;     ad- 
ministration   of    serum 
not  ascertained. 

6 

1 

i 
i 

6 

17  hours 

1 

7 

1 

i 
i 

1 

7 

2  days 

1 

i  Indicates  heavy  precipitate. 
i  Slight  precipitate. 

though  this  method  is  quite  crude  it  is  convenient  for  de- 
tecting the  charge  of  protein  in  the  cerebrospinal  fluid. 

Tables  XXX  and  XXXI  show  some  of  tlie  results  ob- 
tained on  cerebrospinal  fluid  with  the  cataphoresis  experi- 
ment. 

As  is  seen  from  the  tables,  a  considerable  amount  of  the 
protein  in  epidemic  meningitis  moves  toward  the  cathode, 
showing  the  presence  of  positively  charged  protein  in  the 
cerebrospinal  fluid  of  that  disease.  In  tuberculous  menin- 
gitis, however,  the  precipitate  moves  toward  the  anode, 


PATHOLOGIC    CEREBROSPINAL    FLUID  137 

showing  that  the  protein  in  that  case  is  negatively  charged. 
This  again  indicates  the  occurrence  of  specific  biochemical 
changes  in  various  diseases. 

The  Colloidal  Gold  Reaction 

Lange  has  applied  the  work  of  Zsiginondy  who  found 
definite  measures  of  the  protective  action  of  colloids  on 
the  precipitation  of  gold  suspensions  by  sodium  chloride,  to 
the  protein  of  cerebrospinal  fluid.  Lange  found  that  nor- 
mal cerebrospinal  fluid  when  diluted  with  0.4  per  cent  so- 
lution of  sodium  chloride  does  not  aifect  the  solution  of  col- 
loidal gold,  while  pathologic  fluid  produces  characteristic 
changes  for  various  diseases.  Tlie  exact  mechanism  of  the 
gold  chloride  reaction  is  not  well  known,  but  we  have  here 
a  distinct  physicochemical  reaction  that  not  only  signifies 
the  existence  of  a  pathologic  state  of  afl^airs,  but  also  indi- 
cates its  nature  as  this  test  produces  specific  discolorations 
in  certain  diseases. 

Mastic  Reaction 

The  Lange  test  has  been  simplified  by  Emanuel  by  em- 
ploying a  solution  of  mastic,  the  resin  of  the  bark  of  Pis- 
tacia  lentiscus,  a  tree  of  the  Terebinthaceae.  The  mastic 
test  works  on  the  same  principle  as  the  Lange,  and  fur- 
ther corroborates  the  physicochemical  specificity  of  dis- 
ease. 

Ninhydrin  Reaction 

Noble  has  applied  the  ninhydrin  reaction  of  Abderhalden 
to  the  cerebrospinal  fluid  and  found  that  in  tuberculous 
meningitis  a  l)lue  to  a  blue-violet  color  appears  on  boiling 
0.5  to  1  c.c.  of  spinal  fluid  with  O.l  c.c.  of  1  per  cent  ninhy- 
drin solution  for  about  one-half  minute.  Other  workers 
have  confirmed  his  observations. 


138  CEREBROSPINAL  FLUID 

Changes  in  the  Reaction  of  the  Cerebrospinal  Fluid 

Kopetzky  applied  the  acidosis  theory  of  Fischer  to  cere- 
brospinal fluid,  claiming  that  the  fluid  presents  an  acidity 
of  varying  degree  in  all  conditions  Avhich  give  rise  to  pres- 
sure symptoms  of  the  brain.  Kopetzky  used  litmus  paper 
for  his  determination  of  the  reaction  and  he  also  titrated 
the  cerebrospinal  fluid  against  decinormal  sodium  hydrox- 
ide solution.  He  expressed  his  results  in  grains  of  deci- 
normal hydrochloric  acid  solution,  estimated  for  100  c.c. 
of  cerebrospinal  fluid,  using  a  one  per  cent  phenolphthalein 
solution  as  an  indicator. 

I  studied  the  reaction  of  cerebrospinal  fluid  in  disease 
from  various  points  of  view  using  the  titration,  the  H-ion 
concentration  and  the  alkaline  reserve  methods  for  this  pur- 
pose. Originally  I  determined  the  reaction  of  the  cere- 
brospinal fluid  by  titrating  the  fluid  against  n/100  sulphu- 
ric acid.    The  following  method  was  used : 

In  each  of  three  Erlenmeyer  flasks  with  a  capacity  of 
50  c.c,  20  c.c.  of  distilled  water  was  measured,  all  of  the 
flasks  being  of  the  same  height  and  width.  Into  each  flask 
was  put  1  drop  of  a  0.2  per  cent  solution  of  methyl  red.  This 
produced  a  straw-red  color  w^hich  was  the  neutral  point. 
Then  1  c.c.  of  the  fluid  to  be  examined  Avas  placed  in  one  of 
the  flasks  by  means  of  a  graduated  pipette.  This  turned 
the  solution  still  deeper  yellow.  The  flask  was  now 
titrated  with  n/100  sulphuric  acid  until  the  neutral  point 
was  obtained.  This  was  compared  with  the  other  two 
flasks,  all  three  flasks  being  placed  on  a  porcelain  stand. 
When  the  neutral  point  was  reached  the  reading  was  taken 
and  then  one  more  drop  of  the  sulphuric  acid  was  intro- 
duced. A  bright  red  color  appeared.  In  order  to  check 
the  result  1  drop  of  n/100  XaOH  was  added.  This  gave  the 
solution  a  straw  color.  Another  drop  was  added  which 
changed  it  to  yellow,  thus  proving  that  the  end  point  had 
not  been  overrun.  This  procedure  gave  no  difficulty  in 
obtaining  a  sharp  end  point. 


PATHOLOGIC    CEREBROSPINAL   FLUID  139 

With  this  method  it  M^as  found  that  normal  or  nonmenin- 
gitic  fluid  required  between  1.5  and  2.6  c.c.  n/100  to  reach 
the  end  point  which  would  correspond  to  an  alkaline  re- 
serve varying  between  33  and  58  per  cent  total  CO2.  Fluid 
from  epidemic  meningitis  required  between  0.7  and  1.3  c.c. 
of  n/100  sulphuric  acid  which  would  correspond  to  an  al- 
kaline reserve  varying  betw^een  18  and  29  per  cent  total 
CO2  and  fluid  from  pneumococcus  meningitis,  the  same 
amount.  Tuberculous  meningitis,  however,  acted  the  same 
as  nonmeningitic  fluid,  requiring  1.5  to  2.6  c.c.  of  n/100  sul- 
phuric acid  to  reach  the  end  point.     (Table  XXXII.) 

After  I  had  completed  my  investigation  of  the  reaction 
of  the  cerebrospinal  fluid  by  means  of  this  titration  method, 
it  was  realized  that  the  fluid  on  which  the  work  had 
been  done  had  been  standing  too  long  before  examination  to 
give  an  accurate  idea  of  the  real  acidity  of  the  fluid.  I  was 
also  aware  of  the  fact  that  the  titrable  acidity  did  not  rep- 
resent the  true  hydrogen-ion  concentration  of  the  fluid  al- 
though it  does  tell  the  titrable  acidity  or  alkaline  reserve. 
I,  therefore,  decided  to  determine  whether  there  was  a  sim- 
ilar variation  in  the  free  hydrogen-ion  concentration  be- 
tween the  normal  and  meningitic  fluids  of  special  types.  To 
make  the  test  the  gas-chain  method  of  Michaelis  was  used, 
and,  benefiting  by  the  experience  wdth  nonmeningitic  fluid,  I 
endeavored  to  examine  fluid  as  soon  after  removal  from  the 
body  as  possible.  To  carry  out  the  immediate  examination 
it  was  often  necessary  to  resort  to  the  indicator  method, 
using  tlie  Levy-Rowntree-Marriott  standard  and  a  special 
indicator,  checking  both  indicators  by  the  gas-chain  ap- 
paratus. In  over  a  hundred  cases  of  meningitis  examined 
and  checked  by  the  above  methods,  the  following  observa- 
tions were  made : 

Fluid  from  cases  of  tuberculous  meningitis  differed  in 
no  respect  from  that  of  normal  cases,  the  Ph  being  7.4-7.6 
immediately   after   withdrawal    and   ascending   to   8.1    or 


140 


CEREBROSPINAL  FLUID 


Table  XXXII 
TiTRATiox  OF  Cerebrospinal  Fluid  With   diethyl   Red  as   Ixdicator 


DIAGNOSIS 


o 

o      to 

=-"  O   ,  J  u 
--  M  CO  s  g 

S  IS  -  ^  2 
<  g  -.  w 


OTHER    TESTS 


A— xonm?:ningitic 


1 

11  yrs. 

Epilepsy 

2.2  c.c. 

Negative 

2 

12  yrs. 

Typhoid 

2.2 

Negative 

3 

8  yrs. 

Encephalitis   (?) 

2.4 

Negative 

4 

40  yrs 

Lues 

2.2 

Wassermann 
Positive 

5 

Adult 

Cerebrospinal 
lues 

1.8 

Wassermann 
Positive 

6 

Adult 

Insanity 

1.9 

Negative 

7 

Adult 

Insanity 

2.0 

Negative 

8 

Adult 

Xephritis 

2.2 

N^egative 

9 

11  mos. 

Otitis   media, 
pneumonia 

1.5 

Negative 

10 

5\^  mos. 

Erysipelas 

1.9 

Negative 

B— MENINGITIC 


11 

11  yrs. 

Meningococcus 
meningitis 

0.9  c.c. 
Before 
serum 

Increased    pressure. 
41,200   cells,   100% 
polymorphonuclear. 
Meningococci  in 
smear  and  culture. 

After  3 
doses  of 
serum 
acidity 
2.0  c.c. 

12 

10  yrs. 

Meningococcus 
meningitis 

0.9  c.c. 
Before 
serum 

2,400  cells,  99% 
polymorphonuclear. 
Meningococci  in 
smear  and  culture. 

13 

4  yrs. 

Meningococcus 
meningitis 

0.7  c.c. 
Before 
serum 

Several  thousand 
cells  per  c.mm. 
95%   l\^nphocytes. 
Meningococcus  in 
direct  smear  and 
culture. 

After 
serum 
1.5  c.c. 

14 

Pneumococcus 
meningitis 

0.9  c.c. 

Chemical  tests 
positive. 

Pneumococci  in 
culture. 

15 

Pneumococcus 
meningitis 

1.1  c.c. 

Pneumococcus  in 
culture. 

16 

3  yrs 

Tuberculous 
meningitis 

1.9  c.c. 

Tubercle  Itacilli- 
found  in  C.S.  fluid. 

17 

20  mos. 

Tul»ercuIoiis 
meningitis 

2  c.c. 
2.1  c.c. 

All  chemical  tests 
positive.    Autopsy. 

PATHOLOGIC    CEREBKOSPINAL   FLUID 


141 


higher.  In  some  tuberculous  fluids  the  H-ion  concentra- 
tion decreased  in  a  much  shorter  time  than  in  normal 
fluid  (Table  XXXIII). 


H+ 

DONCENTRATIO^f     OF 

Table   XXXIII 
Fluid   prom   Tuberculous 

Meningitis 

No. 

Ph 

Imme- 
diate 

Hour 

1 
Hour 

2 
Hours 

3 
Hours 

4 
Hours 

5 
Hours 

12 
Hours 

18 
Hours 

24 
Hours 

2  Days 
orOver 

1 

8.69(a) 

8.98(a) 
7.9  (a)* 

8.0 +(b) 

2 

3 

7.9  (b) 
8.0  (b) 

4 

8.6  (b) 

5 

8.6  (b) 

6 

7 

8 

9 

10 

7.4  (b) 
7.4  (b) 
7.4  (b) 
7.4  (b) 
7.4  (b) 

8.0  (b) 

8.0 +(b) 

8.2  (c) 
8.2  (c) 

11 

7.6   (c) 

8.2   (c) 

12 
13 

7.4  (b) 

14 

7.4  (c) 

15 

8.0(c)* 

16 

8.1   (c) 

17 

8.0  (c) 

8.8  (a) 

7.8  (c)* 

8.1  (c) 
8.5  (a) 

8.2  (c) 

18 

8.1  (c) 

19 

7.4  (c) 

8.1   (c) 

20 

21 

7.4  (c) 

7.8  (c) 

7.9   (c) 

8.1   (c) 
8.1   (c) 
8.4  (a) 

22 

23 

24 

7.7  (c) 

25 

26 

7.6  (c) 
7.4   (c) 

7.6  (c) 

7.6  (c) 

7.8  (c) 

7.75(a) 
7.7  (c) 

7.8  (c) 

27 

28 

7.4  (c) 

7.6  (c) 

*  Corked 


Fluid  from  cases  of  epidemic  meningitis  showed  an  H-ion 
concentration  slightly  higher  than  that  of  normal,  the  Ph 
being  7.2  to  7.5  immediately  after  withdrawal,  the  average 
being  7.3.  The  greatest  deviation  from  normal,  however, 
was  observed  in  fluid  allowed  to  stand,  the  H-ion  concen- 
tration then  decreasing  slowly  in  some  cases,  remaining 
stationary  in  others,  and  increasing  in  still  others.  Usu- 
ally the  graver  the  condition  of  the  patient,  the  more 
turbid  the  fluid,  and  the  longer  the  retention  of  the  acidity. 
Administration  of  serum  altered  the  H-ion  concentration 
of  the  fluid,  generally  decreasing  it.    Cases  of  pneumococ- 


142 


CEREBROSPINAL  FLUID 


cus  meningitis  showed  a  strong  resemblance  to  those  of 
epidemic  meningitis.  (Tables  XXXIV  and  XXXV.)  (Fig. 
31.) 

The  slightly  higher  H-ion  concentration  of  the  fluid 
in  epidemic  meningitis  as  compared  to  normal,  on  im- 
mediate examination  of  the  fluid,  can  be  explained,  I  be- 
lieve, by  the  bacterial  fermentation  of  the  dextrose  in  the 
fluid  as  indicated  by  the  absence  of  sugar  or  the  les- 
sened amount  of  it  in  meningococcus  meningitis — a  fact 


u 
«♦ 

«.» 
t/ 
11 

W 

17 

7.6 

73 
1.1 

"" 

*i- 

*V 

^   ■ 

- 

S'^' 

^.'^'^ 

"^'■f 

r'f'^ 

Ij^O 

seit 

Q)^ 

_^, 

.v,>?j 

No-^" 

p-1 

ni^"- 

_^ 

,-■ 

■   ^ 

^- 

-''' 

1 

/ 

'-"■ 

JP' 

..».< 

men 

,ng.t 

It.  no 

scru 

mg.. 

1 ^^ 

mi 

1 

* — 

— 

^ 

{7/ 

7^ 

^^ 

— t 

:><de 

^.C-r 

<iti^ 

1 1 

mg 

b; 

III) 

1  , 

1  ff 

n.T,^,,.,  V 

1        a       3       4       5       fc       7        g       ")       10       II       12      13     (4       15      16      n      18       19      20     1\     r\ 
Hours                                                                                                                                                                                 1 

Fig.   31. — Change  in  the  H+  concentration  of  three  types  of  cerebrospinal  fluid. 

that  has  been  brought  out  by  several  investigators.  As  for 
the  mechanism  responsible  for  the  slow  decrease  in  the  H- 
ion  concentration  of  epidemic  fluid,  there  are  several  possi- 
bilities to  be  considered,  such  as  a  slower  loss  of  CO2  in  the 
fluid  upon  standing,  a  constant  CO2  production  by  the  cells 
present  in  the  sediment  of  the  fluid;  lactic  acid  formation 
due  either  to  further  fermentation  of  sugar  by  the  bacteria 
in  the  test  tube  or  to  a  destruction  of  the  cells  on  standing 
of  the  fluid. 


PATHOLOGIC    CEREBROSPINAL   FLUID 


143 


Table  XXXIV 

H+     Concentration  of  Fluid   of  Epidemic  Meningitis  Before  Administration 

OF   Serum 


,Ph 

No. 

Imme- 
diate 

Hour 

1 
Hour 

2 
Hours 

3 
Hours 

4 
Hours 

5 
Hours 

12 
Hours 

18 
Hours 

24 
Hours 

2  Days 
orOver 

1 

7.4  (b) 

2 
3 

7.4  (b) 

7.0  (b) 

4 

7.1   (c) 
7.3  (c) 

7.8  (c) 

5 

7.7  (c) 

7.8  (c) 

6 

/f.  . 

7.4  (c) 

7 

7.2  (c) 

8 

7.1   (c) 

9 

.    .    . 

7.9  (c) 
7.9  (c) 

7.8  (c) 

7.4  (c) 
7.7  (c) 

7.6  (c) 

10 

11 

7.4  (c) 

12 

13 

7.2  (c) 

7.3  (c) 
7.3  (c) 

7.2  (c) 

7.1  (a) 

14 

15 

7.2  (c) 

16 

7.8  (c) 

17 

7.7  (c) 
7.7  (a) 

7.6  (c) 

18 

7.3  (c) 

7.4  (c) 

7.9  (c) 

19 

6.6  (c) 

20 

7.4— (c) 
7.5 

7.3— (c) 
7.4 
7.3  (c) 

8.1  (c) 

7.8  (c) 
7.8  (a) 

7.8  (a) 

7.9  (c) 

6.0  (a) 

21 

22 

Table  XXXV 

H-IoN  Concentration  op  Fluid  op  Epidemic  Meningitis  After  Administration 

OF  Serum 


Ph 

No. 

Imme- 
diate 

Hour 

1 
Hour 

2 
Hours 

3 
Hours 

4 
Hours 

5 
Hours 

12 
Hours 

18 
Hours 

24 
Hours 

2  Days 
orOver 

1 
2 
3 
4 

7.4— (b) 
7.4— (b) 
7.4— (b) 

7.0  (b) 

6 

7.4  (b) 

6 

* 

7.4  fb) 
1.4  Cb) 

7.1   (c) 

7 

7.0  (b) 

8 

7.1  (b) 

9 

10 

7.4   (c) 

7.6  (c) 

7.8  (c) 

11 
12 

7.3  (c) 

7.7   (c) 

13 

14 

7.2  (a 

16 

7.1   (c) 

7.9  (c) 
8.1* 

8.2 

7.7  (c) 

16 

17 

7.3  (c) 

7.6—7 
(c) 

7.7— 
(c) 

7.7—7.8 
(c) 

18 

7.4 

*  Diagnosis  was  not  settled. 


144 


CEREBROSPINAL  FLUID 


I  found  that  the  H-ion  concentration  of  these  fluids  in- 
creased from  7.4  to  7.0  upon  standing  in  tubes  tightly 
corked,  thus  indicating  that  tliere  is  not  only  no  loss  of  CO2, 
but  that  there  is  also  a  formation  of  certain  acids  on  stand- 
ing. Nonmeningitic  and  tuberculous  fluids  give  quite  dif- 
ferent results  (Tables  XXXVI  and  XXXVII).    (Fig.  32.) 

With  the  view  of  further  ascertaining  the  cause  of  this 
increase  of  acidity  the  following  experiments  were  made: 


Pm 

?•• 

u 

X% 
7.7 
It, 
7.S 
7.4 
73 
7.2 
71 
7.0 

1 

--^ 

■ ' 

/- 
„/ 

t"^* 

.V 

^  "^ 

1 

^ 

r      1 

X^ 

^ 

>-V 

U 

^ 

\ 

-    - 

^■4- 

^ 

^ 

-    - 

•■  n  n 

■^±. 

''4 

zk. 

219b 

< 

\r 

\. 

■^P' 

x^ 

^i 

^ 

^ 

^ 

'  "^ 

2     4      (>     8     10     12     14     lb     IX     20    n    I* 
Howrs 

Fig.  32. — Different  effects  of  corking  on  tuberculous  and  epidemic  fluids.  Case  219a, 
tuberculous  meningitis,  cotton  plugged;  b,  same  ffuid,  tightly  corked  (no  air  above). 
Case  232a,  tuberculous  meningitis,  cotton  plugged;  b,  same  fluid,  corked  (no  air  above). 
Case  223a,  epidemic  meningitis,  cotton  plugged;  b,  same  fluid,  tightly  corked  (no  air 
above);  Case  230a,  epidemic  meningitis,  cotton  plugged;  b,  same  fluid,  tightly  corked 
(no  air  above.) 


In  one  chamber  of  the  biometer  (Tashiro)  was  put  1  c.c. 
of  tuberculous  meningitic  fluid,  and  exactly  the  same 
amount  of  epidemic  fluid  in  the  other  chamber.  It  w^as 
found  that  the  tuberculous  fluid  gave  off  more  CO2  than 
the  epidemic,  showing  that  although  both  tuberculous  arid 
epidemic  fluids  give  off  CO2  constantly,  tuberculous  fluid 


PATHOLOGIC    CEREBROSPINAL   FLUID 

Table  XXXVI 
Tuberculous  Fluid,  Corked 


145 


FLUID 

DATE  DRAWN 

DATE 
EXAMINED 

INTERVAL 

HOW 
STOPPERED 

Ph 

B. 

6/28/17 
9:10 

7.4 

B. 

6/28/17 
3:05 

5  hours 

Cork 

7.4 

B. 

6/28/17 
3:05 

5  hours 

Cotton 

7.9 

A.  C. 

7/13/17 
11a.  m. 

7/13/17 
11  a.  m. 

Immediately 

7.5-6 

7/13/17 

7/14/17 
11  a.  m. 

24  hours 

Cork 

7.5-6 

7/13/17 

7/14/17 
11  a.  m. 

24  hours 

Cotton 

8.0 

Table  XXXVII 
Fluid  from  Epidemic  Meningitis,  with  Cork  and  Cotton  Stopper 


DIAGNOSIS 

DATE 

DATE 

INTERVAL 

stoppered 

Ph 

DRAWN 

EXAMINED 

WITH 

Epidemic 

6/30/17 

6/30/17 

Immediate 

7.3 

meningitis 

12:20  p.m. 

12:20  p.m. 

6:35  p.m. 

G}4  hours 

Paraffined  cork 

7.0 

6:35  p.m. 

6}4  hours 

Cotton  plug 

7.7 

Epidemic 

7/6/17 

7/6/17 

Immediate 

7.4 

meningitis 

2:30  p.m. 

2:30  p.m. 

7/7/17 

18  hours 

Paraffined  cork 

7.3 

8:30  a.m. 

7/7/17 

18  hours 

Cotton 

8.2 

8:30  a.m. 

Epidemic 

7/11/17 

7/11/17 

Immediate 

7.4-7.5 

meningitis 

11:30  a.m. 

7/12/17 

17  hours 

Paraffined  cork 

7.4 

4:30  p.m. 

4:30  p.m. 

17  hours 

Cotton 

8.1 

Epidemic 

7/11/17 

7/11/17 

Immediate 

7.3-7.4 

meningitis 

1:30  p.m. 

1:30  p.m. 

7/12/17 

7:30  a.m. 

18  hours 

Paraffined  cork 

7.0 

18  hours 

Cotton 

7.8 

Epidemic 

7/14/17 

7/14/17 

Immediate 

7.3 

meningitis 

7/15/17 

22  hours 

Paraffined  cork 

7.1 

22  hours 

Cotton 

7.9 

146  CEREBROSPINAL  FLUID 

loses  more  CO2  than  does  epidemic.  This  suggests  that 
the  increased  acidity  in  epidemic  meningitis  is  not  due  to 
a  greater  production  of  CO2  but  probably  to  the  production 
of  some  other  acid,  very  likely  lactic  acid. 

Further  work  on  the  subject  showed  a  greater  amount 
of  lactic  acid  in  the  fluid  of  epidemic  and  other  forms  of 
suppurative  meningitides  than  in  that  of  normal  or  of  tu- 
berculous meningitis.  Furthermore,  upon  standing,  the 
fluid  of  suppurative  meningitides  showed  an  increase  in  its 
lactic  acid  content.  This  was  more  marked  in  the  fluids 
that  contained  many  polymorphonuclear  leucocytes.  Many 
fluids  that  showed  no  acetone  immediately  after  with- 
drawal, showed  traces  of  it  when  allowed  to  stand  for  a 
day  or  two.  These  changes  indicate  that  the  increase,  on 
standing,  of  the  H-ion  concentration  of  fluids  from  sup- 
purative meningitides  is  due  to  a  constant  formation  of 
organic  acids,  resulting  from  the  decomposition  of  the  cells 
in  the  fluid. 

BACTERIOLOGIC 

Cerebrospinal  fluid  is  sterile,  even  after  it  has  passed 
through  the  nose  as  suggested  by  the  cases  reported  in  the 
literature.  Any  bacteria  in  the  fluid,  is,  therefore,  indica- 
tion of  the  existence  of  some  pathologic  process  in  the  body, 
unless  it  is  knoAm  that  the  bacteria  are  the  result  of  some 
external  contamination  of  the  fluid  after  its  removal. 

The  cerebrospinal  fluid  is  one  of  the  best  mediums  for 
the  groM'th  of  bacteria.  They  grow  in  it  luxuriantly. 
However,  at  times  it  is  very  difficult  to  isolate  the  bacteria 
from  the  fluid.  Some  bacteria,  such  as  the  pneumococcus 
and  streptococcus  grow  easily  on  ordinary  culture  media; 
others,  notably  meningococci  and  influenza  bacilli  grow 
only  on  speciaL media  and  at  that  with  difficulty,  while  still 
others,  like  the  tubercle  bacilli  can  hardly  be  grown  at  all. 


PATHOLOGIC    CEREBROSPINAL   FLUID  147 

IMMUNOLOGIC 

Immunology  has  thrown  a  great  deal  of  light  on  the 
diagnosis  and  pathology  of  diseases  related  to  the  nervous 
system.  The  various  agglutination  tests  help  to  differenti- 
ate the  various  types  of  meningococci.  The  hemolysin  re- 
action indicates  a  permeability  of  the  meninges.  The  neu- 
tralization test  assists  in  the  diagnosis  of  poliomyelitis,  and 
the  Wassermann  test  is  an  invaluable  aid  in  the  diagnosis  of 
syphilis  of  the  nervous  system. 

Agglutination 

The  agglutination  test  is  based  on  the  principle  that 
various  bacteria  agglutinate  when  they  are  brought  into 
contact  with  their  respective  sera.  This  principle  is  uti- 
lized for  the  identification  of  meningococci  and  pneumo- 
cocci. 

Hemolysin 

It  has  been  found  by  a  number  of  observers  that  normal 
cerebrospinal  fluid  contains  no  antisheep  hemolysin, 
whereas  the  spinal  fluid  in  some  cases  of  meningitis  and 
poliomyelitis  has  been  found  to  contain  hemolysin.  The 
hemolysin  test  is  of  value  as  corroborative  evidence  of  an 
inflammation  of  the  meninges  although  the  results  of  the 
test  up  to  date  are  not  constant  enough  to  be  of  diagnostic 
value. 

Hauptmann  found  that  the  cerebrospinal  fluid  of  patients 
suffering  from  lesions  of  the  central  nervous  system  in- 
hibits the  hemolysis  of  erythrocytes  which  is  usually  pro- 
duced by  a  solution  of  saponin.  He  considers  the  inhibi- 
tion of  hemolysis  in  cases  of  this  kind  to  be  due  to  choles- 
terin  produced  by  the  degeneration  of  nervous  tissue. 


148  CEREBROSPINAL  FLUID 

Wassermann  Reaction 

The  Wassermann  reaction  has  done  a  great  deal  to 
change  our  conception  of  diseases  in  general  and  of  syph- 
ilis in  particular.  Most  authors  consider  a  positive  Was- 
sermann test  of  the  cerebrospinal  fluid  to  be  specific  for 
syphilis  of  the  central  nervous  system.  Positive  tests  are 
reported  to  have  been  found  in  the  fluid  of  otlier  condi- 
tions, such  as  leprosy  and  beriberi,  still  it  is  practically 
pathognomonic  of  lues,  especially  in  harmony  with  the  clin- 
ical condition  and  the  history  of  the  case.  A  negative  AYas- 
sermann,  however,  does  not  always  rule  out  syphilis. 

Bibliography 

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fliissigkeit,  Arch.  f.  Psych.,  1908,  xliv,  2. 
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XX,  1109. 
Boyd:      The   Clinical   Importance   of   Cerebrospinal   Fluid,   Brit.   Med.    Jour., 

1914,  i,  961. 
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Tliese  de  Geneve,  1905. 
Cimbal:     Chem.,  physikal.  u.  morpholog.  Ergehnisse  an  240  Spinalpunktionen 

und  deren  diagnostische  und  therapeutische  Vervvertung;  Thorap.  d.  Ge- 

gemv.,  1906. 
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fliissigkeit  bei  Epilepsie  u.  organischen  Erkrankungen  des  Nervensystems, 

Ztschr.  f.  physiol.  Chem.,  1903,  xxxix,  526. 
Donatli :   Die  Phosphorsauregehalt  der  Cerebrospinalfliissigkeit  bei  verschiede- 

nen  Nervenkrankheiten,  Ztschr.  f.  physiol.  Chem.,  1904,  xlii,  141. 
Grunberger:     tJber  den  Befund  von  Acetessigsaiire  in  der  Zerebrospinalfliissig- 

keit  bei  Coma  diabeticum,  Ztschr.  f.  inn.  Med.,  1905,  xxv,  617. 
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dans  1©  liquide  cephalo-rachidien  des  paralvtiques  generaux,  Eev.  neurol., 

1903,  xi,  406. 
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iv,  23. 
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bei  organischen  Nervenkrankheiten,  Med.  Klin.,  1910.  vi,  181. 
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Cerelirospinal  Meningitis,  Jour.  Am.  Med.  Assn.,  1918,  Ixxi,  612. 
Kauflfman:      u])er   angeblichen   Befund   von   Cholin   in   der  Lumbalfliissigkeit, 

Neurol.  Centralbl.,  1908,  xx,  966. 
Kcpetzky:     Meningitis,  Nature,  Cause,  Diagiiosis,  and  Princijdes  of  Surgical 

Relief,  Manhattan  Eye,  Ear  and  Throat  Hospital  Reports,  1913. 
Landois:     Lehrbuch  der  Physiologic. 


PATHOLOGIC    CEREBROSPINAL   FLUID  149 

Launois  et  Bouhul :  Sur  la  Teneur  en  sucre  du  liquide  cephalo-rachidien, 
Rev.  neurol.,  May,  1904. 

Lockemann:  Nachwcis  von  Fleisehmilchsaiire  im  Blut,  Urin  und  Cerebro- 
spinalfliissigkeit,  Miinchen  med.  Wchnschr.,   1906,  liii,  299. 

Latiner:  Das  Veihalten  des  Reduktionsindex  in  dem  normalen  und  patho- 
logischen  Zerel)rosipinalflussigkeit,  Wien.  klin.  Wchnschr.,  1911,  xxiv,  783. 

Mayerhofer :  Ziir  Charakteristik  und  Differential  Diagnose  des  Liquor  Cere- 
brospinalis,  Wien.  klin.  Wchnschr.,  1910,  xxiii,  651. 

Mott  and  Halliburton:  The  Chemistry  of  Cerebrospinal  Fluid,  Lancet,  Lon- 
don, 1901. 

Myers:  The  Cerebrospinal  Fluid  in  Certain  Foniis  of  Insanity  W^ith  Special 
Reference  to  the  Content  of  Potassium,  Jour.  Biol.  Chem.,  1909,  vi,  115. 

Pighihi:  tjber  den  Cholesteringehalt  der  Lumbalfliissigkeit  einiger  Geistes- 
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Deutsch.  Ztschr.  f.  Nervenh.,  1911,  xlii,  279. 

Rubenstone:  Cerebrospinal  Fluid  and  Its  Diagnostic  Significance,  New- 
York  Med.  Jour.,  1913,  xcviii,  1210. 

Tashiro:     Chemical  Sign  of  Life,  Chicago,  1917. 

Thomson:  A  Note  on  Certain  Peculiar  Crystals  Found  in  the  Cerebrospinal 
Fluid  from  a  Case  of  Septic  Meningitis,  Lancet,  London,  1915,  653. 

Zsigmondy:     Colloids  and  the  Ultramicroscope,  New  York,  1909. 


CHAPTER  VI 

METHODS  OF  EXAMINATION  OF  CEREBROSPINAL 
FLUID  FOR  DIAGNOSTIC  PURPOSES 

In  the  following  pages  I  shall  outline  the  methods  em- 
ployed in  the  examination  of  cerebrospinal  fluid  for  the 
purpose  of  detecting  the  presence  of  pathologic  processes. 
I  shall  describe  only  those  methods  that  have  been  proved 
to  be  both  simple  and  practical. 

PHYSICAL 

No  special  apparatus  is  required  for  the  physical  exami- 
nation of  the  cerebrospinal  fluid  with  the  exception  of  that 
used  for  the  determination  of  the  pressure  of  the  fluid. 
All  other  physical  examinations  can  be  made  by  the  naked 
eye.  The  amount  of  fluid  withdrawn  can  be  measured 
either  in  a  graduate  or  it  may  be  estimated.  If  the  amount 
of  fluid  easily  withdraMii  from  the  patient  in  recumbent 
position  exceeds  10  c.c.  a  pathologic  condition  should  imme- 
diately be  suspected  and  the  fluid  carefully  examined. 

Color 

The  color  of  the  fluid  furnishes  one  of  the  best  indica- 
tions of  the  existence  of  an  abnormal  condition.  Normal 
fluid  in  its  natural  state  is  colorless.  Any  change  in  color 
is  therefore  significant.  The  best  way  to  examine  the 
fluid  for  color  is  to  hold  it  up  against  the  light  with  a 
background  of  black  or  yellow.  The  glass  of  the  tube  con- 
taining the  fluid  should  be  thin  enough  to  show  the  color 
clearly  and  the  tube  itself  should  always  be  kept  in  the  same 
position  toward  tlie  light.  Daylight  naturally  is  better  for 
the  observation  of  color  than  artificial  light.     The  specific 

150 


EXAMINATION    FOR   DIAGNOSTIC    PURPOSES  151 

changes  of  color  in  different  conditions,  in  the  various  types 
of  meningitis,  and  in  conditions  known  as  xanthochromia 
and  in  jaundice,  will  be  described  under  their  respective 
headings. 

Foam 

If  only  five  or  ten  c.c.  of  fluid  is  removed  the  tube  con- 
taining the  fluid  should  be  shaken  and  watched  for  the 
formation  of  foam.  The  length  of  time  the  foam  persists 
should  be  observed,  and  its  character  noted,  as  both  fur- 
nish a  clew  as  to  the  presence  and  intensity  of  pathologic 
processes. 

If  more  than  10  c.c.  is  removed,  the  first  tube,  containing 
2  to  3  c.c,  should  be  put  away  for  various  examinations 
(Cf.  Chapter  III).  The  second  tube,  containing  3  to  5  c.c, 
should  be  left  undisturbed  for  pellicle  formation.  The 
third  tube,  containing  preferably  between  9  and  10  c.c,  al- 
though 5  c.c.  will  also  do,  should  be  tested  for  foam  for- 
mation. After  the  foam  has  subsided,  the  fluid  in  this  tube 
may  be  used  for  any  purpose  desired. 

Pellicle 

In  looking  for  a  pellicle,  one  must  be  careful  not  to  dis- 
turb the  fluid.  It  is  therefore  best  to  put  the  tube  aside 
for  this  purpose,  as  soon  as  the  fluid  is  collected.  As  for 
the  best  conditions  under  which  a  pellicle  will  form,  no  set 
rules  can  be  given.  Generally,  a  pellicle  will  form  either 
at  room  temperature  or  in  the  cold.  My  experience  has 
shown  that  a  pellicle  forms  more  easily  at  room  temper- 
ature than  on  ice.  Hence,  the  tube  in  which  the  pellicle  is 
expected  to  form  should  be  left  at  room  temperature,  abso- 
lutely undisturbed.  Another  point  is  that  the  pellicle 
must  be  examined  not  later  than  twenty-four  hours  after 
the  withdrawal  of  the  fluid,  as  autolysis  often  takes  place, 
so  that  the  pellicle  undergoes  changes  on  standing  for  two 
or  three  days. 


152  CEREBROSPINAL  FLUID 


CHEMICAL 


Many  qualitative  and  quantitative  chemical  tests  have 
been  used  by  various  scientific  workers.  Not  all  of  the 
tests,  however,  are  necessary  or  applicable  for  routine  diag- 
nostic purposes. 

The  quantitative  determination  of  urea  may  be  of  value, 
as  urea  has  been  found  to  be  greatly  increased  in  the  cere- 
brospinal fluid  in  cases  of  uremia  and  nephritis  and  at 
times  also  in  arteriosclerosis.  However,  since  the  urea  con- 
tent of  the  blood  is  also  greatly  increased  in  these  condi- 
tions it  is  best  to  reserve  this  test  for  the  determination  of 
urea  in  the  blood  and  to  keep  the  fluid  for  other  tests. 

The  determination  of  phosphates  has  not  been  found 
practical  because  of  its  uncertain  diagnostic  value. 

The  chemical  examinations  of  the  cerebrospinal  fluid  for 
diagnostic  purposes  should  therefore  be  limited  to  albumin 
and  globulin  tests,  permanganate  index,  sugar,  and  chlo- 
rides. In  a  rapid  examination  of  the  fluid  all  but  the  glob- 
ulin test  may  be  dispensed  with  as  the  globulin  increase  is 
the  one  factor  common  to  all  inflammatory  processes, 
whereas  the  sugar  and  chloride  content  often  remain  un- 
changed. In  making  the  chemical  tests  one  should  make 
sure  that  all  the  vessels  employed  are  chemically  clean. 

Increase  of  Protein 

A  number  of  qualitative  tests  have  been  described  for 
the  detection  of  an  increase  in  protein.  One  is  the  acetic 
acid  test  of  Moritz  which  consists  of  tlie  addition  of  a  few 
drops  of  a  5  per  cent  acetic  acid  solution  to  2  c.c.  of  cere- 
brospinal fluid.  If  a  precipitate  forms,  an  increase  of  pro- 
tein is  indicated.  Another  one  is  the  nitric  acid  test.  A 
few  drops  of  nitric  acid  are  added  to  the  fluid,  and  a  heavy 
cloud  is  produced  if  the  protein  content  is  increased.    How- 


EXAMINATION    FOR    DIAGNOSTIC    PURPOSES  153 

ever,  neither  of  these  two  tests  is  employed  to  any  great 
extent. 

The  quantitative  protein  determination  lias  been  used  by 
various  workers  for  the  diagnosis  of  meningitis  and  other 
pathologic  conditions.  Bybee  and  Lorenz  employed  the 
Brandenburger  method  for  urinalysis  for  the  determination 
of  albumin,  Mestrezat  used  a  coloriinetric  method  for  this 
purpose.  Probably  the  simplest  method  for  the  determi- 
nation of  albumin  in  cerebrospinal  fluid  is  the  following:  A 
glass  tube,  five  to  six  millimeters  in  diameter  and  six  to 
six  and  one-half  inches  in  length  is  stripped  by  a  piece  of 
adhesive  plaster,  or  fastened  by  a  rubber  band  to  an  Es- 
bach  albuminometer.  The  small  tube  is  filled  with  cerebro- 
spinal fluid  to  a  level  corresponding  to  mark  *'U"  on  the 
Esbach  tube,  and  with  tlie  Esbach  reagent  to  a  level  corre- 
sponding to  mark  ''R"  on  the  albuminometer.  The  two 
tubes  are  allowed  to  stand  for  twenty-four  hours,  and  the 
amount  of  precipitate  in  the  small  tube  is  then  read  off  on 
the  Esbach  albuminometer,  the  result  being  expressed  in 
grams  of  albumin  per  liter. 

GLOBULIN  TESTS 

Several  globulin  tests  have  been  proposed.  Among  the 
most  important  of  them  are  the  Noguchi,  Ross-Jones,  Non- 
ne-Apelt,  the  Pandy,  and  the  sulphosalicylic  mercuric  chlo- 
ride tests.  In  doing  any  globulin  test  one  must  make  sure 
at  the  beginning  that  the  fluid  is  perfectly  free  of  blood. 
Should  there  be  any  blood  present  in  the  fluid  the  globulin 
test  will  be  positive  even  if  no  pathologic  process  exists. 
The  effect  of  centrifugation  on  the  fluid  is  not  marked.  I 
found  very  little  difference  between  the  globulin  reaction 
of  centrifuged  and  uncentrifuged  specimens.  The  cells 
present  in  the  fluid  neither  interfered  with  nor  accelerated 
the  positiveness  of  the  globulin  test.  A  description  of  the 
various  globulin  tests  follows: 


154  CEREBROSPIISrAL  FLUID 

Noguchi 

Two-tenths  c.c.  of  cerebrospinal  fluid  is  transferred  by 
means  of  a  pipette  to  a  small  test  tube,  preferably  a  regular 
Noguchi  tube.  Five-tenths  c.c.  of  butyric  acid  solution  (5 
c.c.  of  butyric  acid  to  45  c.c.  of  physiologic  salt  solution)  is 
added  to  the  fluid;  this  mixture  is  boiled  for  a  few  seconds 
and  0.1  c.c.  of  a  4  per  cent  aqueous  NaOH  solution  is 
poured  into  it  and  it  is  boiled  again  for  a  few  seconds.  If 
there  is  an  increase  in  the  globulin  of  the  fluid  a  fine  or 
coarse  granular,  flocculent  deposit  is  formed  in  from  five 
to  twenty  minutes.  If  no  flocculence  makes  its  appearance 
within  two  hours,  or  if  nothing  more  than  a  slight  opales- 
cence is  present,  it  shows  that  the  globulin  is  not  increased. 

Ross-Jones 

The  Ross-Jones  test  consists  of  the  superimposition  of 
0.3  c.c.  of  a  saturated  solution  of  ammonium  sulphate  upon 
an  equal  amount  of  cerebrospinal  fluid.  The  ammonium 
sulphate  solution  is  prepared  in  the  following  manner:  85 
grams  of  ammonium  sulphate  is  put  into  100  c.c.  of  water 
and  boiled  in  an  Erlenmeyer  flask  until  no  more  salt  goes 
into  solution.  This  is  then  filtered  and  used  for  the 
test.  If  the  solution  has  an  acid  reaction  the  results  will 
not  be  accurate.  If  the  globulins  in  the  fluid  are  increased 
an  opaque  ring  develops  at  the  point  of  contact  of  the  fluid 
and  ammonium  sulphate. 

Nonne-Apelt 

Phase  I. — The  constituents  used  for  the  Nonne-Apelt  test 
are  the  same  as  those  used  for  the  Ross-Jones,  except  that 
equal  parts  of  the  cerebrospinal  fluid  and  saturated  am- 
monium sulphate  are  mixed  instead  of  being  superimposed 
one  upon  the  other.  A  white  precipitation  forms  in  three 
minutes  if  the  reaction  is  positive  (euglobulin). 

Phase  II. — The  precipitate  is  filtered,  one  drop  of  a  10 
per  cent  acetic  acid  is  now  added  to  the  filtrate  and  the 


EXAMINATION   FOR   DIAGNOSTIC   PURPOSES  155 

mixture  is  boiled.     A  precipitation  forms  if  the  reaction 
is  positive  (serum  albumin). 

Zaloziecki  has  modified  the  Nonne  test,  Phase  I,  in  that 
he  uses  only  0.5  c.c.  of  cerebrospinal  fluid  instead  of  the 
original  method  of  using  2  c.c.  It  has  been  found  that  0.5 
c.c.  is  just  as  accurate  as  is  2  c.c. 

Kaplan  Method 

Five-tenths  c.c.  of  cerebrospinal  fluid  is  heated  and  boiled 
twice.  Then  3  drops  of  a  5  per  cent  solution  of  butyric 
acid  in  physiologic  salt  solution  is  added  to  the  test  tube 
and  is  followed  immediately  by  0.5  c.c.  of  a  supersaturated 
solution  of  ammonium  sulphate.  The  mixture  is  now  set 
aside  for  20  minutes.  An  excess  of  globulin  is  indicated  by 
a  thick  granular  precipitate. 

Pandy 

One  drop  of  cerebrospinal  fluid  is  added  to  one  c.c.  of  a 
concentrated  solution  of  carbolic  acid  (1  part  of  phenol 
crystals  to  15  parts  of  water).  A  bluish  white  ring  or  cloud 
results  if  an  excess  of  globulin  is  present. 

Sulphosalicylic  Mercuric  Chloride  Method 

One  c.c.  of  cerebrospinal  fluid  is  introduced  into  each  of 
two  small  tubes  of  uniform  height  and  width,  (about  0.3 
cm.  in  diameter) ;  into  one  of  the  tubes  1  c.c.  of  a  3  per  cent 
sulphosalicylic  acid  is  introduced,  and  into  the  other  1  c.c. 
of  a  1  per  cent  mercuric  chloride.  If  the  fluid  is  pathologic, 
a  heavy  precipitate  forms  in  the  tube  containing  the  sulpho- 
salicylic acid;  if  the  fluid  is  normal  only  a  slight  turbidity 
appears.  The  tubes  are  then  allowed  to  stand  for  twenty- 
four  hours,  after  which  the  sediment  in  them  is  measured 
and  comjjared.  Under  normal  conditions  the  sediment 
found  after  24  hours  in  either  of  the  two  tubes  is  very 
slight ;  in  all  suppurative  meningitides,  however,  the  precip- 


156  CEREBROSPINAL  FLUID 

itation  \\nth  the  sulphosalicylic  is  very  heavy,  often  being 
three  times  the  size  of  the  precipitation  obtained  with  the 
mercuric  chloride.  In  tubercuhjus  meningitis,  the  opposite 
reaction  takes  place,  the  precipitation  with  the  mercuric 
chloride  usually  being  three  times  as  heavy  as  that  obtained 
wiih  sulphosalicylic  acid. 

Relative  Value  of  the  Globulin  Tests 

It  would  be  well  to  emphasize  the  fact  that  there  is  no 
one  test  for  the  diagnosis  of  pathologic  conditions  that  can 
be  considered  absolutely  final.  Furthermore,  even  all  the 
tests  together  are  at  times  unreliable,  unless  supported  by 
additional  observations.  A  careful  worker  soon  learns  that 
to  make  a  correct  diagnosis  he  must  take  into  account  the 
entire  picture  of  the  disease  gained  from  both  clinical  and 
laboratory  observations.  There  are  so  many  possibilities 
for  error  in  laboratory  work  that  unless  one  combines  the 
clinical  with  the  laboratory  results,  he  is  apt  to  arrive  at 
erroneous  conclusions.  As  for  the  relative  value  of  the  dif- 
ferent tests,  the  experience  of  different  workers  varies.  I 
found  the  sulphosalicylic  mercuric  chloride  test  the  most 
helpful  chemical  or  physicoehemical  test  in  the  diagnosis 
of  tuberculous  meningitis.  Early  in  the  course  of  the  dis- 
ease when  other  tests  could  not  be  depended  on  for  definite 
results  this  test  gave  a  positive  reaction  in  the  diagnosis  of 
tuberculous  meningitis.  Many  of  my  colleagues  report  a 
similar  experience  with  this  test.  Of  the  other  globulin 
tests,  the  Noguchi  has  been  found  the  most  reliable.  The 
Ross-Jones  has  at  times  been  known  to  give  a  negative  reac- 
tion when  the  other  tests  showed  a  positive  reaction.  The 
Nonne,  Phase  I,  is  not  so  sensitive  as  the  Noguchi  or  even 
the  Ross-Jones  although  with  a  well-prepared  ammonium 
sulphate  solution  the  test  is  fairly  reliable.  As  for  the 
Pandy,  it  is  very  sensitive,  but  at  times  it  precipitates  even 
normal  cerebrospinal  fluid  so  that  one  is  often  at  a  loss  to 
know  what  is  the  borderline  between  normal  and  patho- 
logic fluid. 


EXAMll^ATlOlSr   FOR   DIAGNOSTIC   PURPOSES  157 

The  Permanganate  Test 

The  test  was  descrihed  by  Mayerhofer  in  1910  for  the 
determination  of  organic  substances  in  cerebrospinal  fluid, 
the  method  having  originally  been  described  by  Kubel- 
Thiemich  for  the  determination  of  organic  substances  in 
water.  Mayerhofer  showed  that  every  cerebrospinal  fluid 
oxidizes,  or,  as  he  termed  it,  reduces,  permanganate,  and 
that  fluid  in  cases  of  meningitis  has  a  higher  oxidation  in- 
dex than  normal  fluids  or  even  those  of  meningism. 

One  c.c.  of  cerebrospinal  fluid  is  introduced  into  an  Er- 
lenmeyer  flask  by  an  accurately  graduated  pipette;  50  c.c. 
of  distilled  water  and  10  c.c.  of  diluted  H2SO4  (1  part 
H2SO4  and  three  parts  H2O)  are  added,  and  the  mixture  is 
brought  to  a  boiling  point;  10  c.c.  of  a  decinormal  perman- 
ganate solution  is  then  introduced  into  the  flask  and  the  so- 
lution is  boiled  for  exactly  ten  minutes.  At  the  end  of  this 
time  10  c.c.  of  decinormal  oxalic  acid  is  put  into  the  flask, 
whereupon  the  red  or  yellowish-red  color  turns  white.  Ti- 
tration is  now  carried  on  drop  by  drop  from  a  burette  con- 
taining the  permanganate  solution  until  the  color  of  the  so- 
lution in  the  receptacle  turns  red  and  remains  so  for  a  num- 
ber of  minutes.  The  number  of  cubic  centimeters  of  per- 
manganate required  to  produce  the  end  reaction  is  then 
read  off  and  the  figure  is  taken  as  the  permanganate  index. 
In  doing  this,  one  must  make  certain  that  10  c.c.  of  n/10 
permanganate  equals  10  c.c.  of  n/10  oxalic  acid.  It  is  also 
necessary  to  ascertain  how  much  permanganate  is  required 
to  oxidize  the  water  and  the  II2SO4  and  this  amount  should 
be  subtracted  from  the  number  of  cubic  centimeters  of  per- 
manganate required  to  oxidize  the  cerebrospinal  fluid  solu- 
tion. For  example,  if  4  c.c.  of  n/10  permanganate  was  re- 
quired for  the  cerebrospinal  fluid  and  0.5  c.c.  permanganate 
for  water  and  H2SO4,  the  0.5  c.c.  should  be  subtracted  from 
the  whole  number,  leaving  the  reduction  index  only  3.5. 
Boveri  simplified  the  permanganate  test.  He  uses  1  c.c.  of 
cerebrospinal  fluid  and  1  c.c.  of  a  1  per  cent  permanganate 


158  CEREBROSPIXAL  FLUID 

solution.  If  the  cerebrospinal  fluid  is  normal,  there  is  no 
change  of  color  on  contact  of  the  fluid  with  the  perman- 
ganate. In  all  pathologic  fluids,  a  yellow  ring  forms  on 
contact.  When  the  fluid  and  the  permanganate  solution 
come  into  contact,  the  change  in  color  appears  in  a  few  sec- 
onds or  at  most  in  a  few  minutes.  The  quicker  the  reac- 
tion, the  more  pathologic  the  fluid. 

Sugar 

The  qualitative  determination  of  sugar  in  the  cerebro- 
spinal fluid  by  Fehling's  solution  is  of  no  special  diagnos- 
tic importance  as  by  this  method  only  an  absence  of,  but 
not  a  decrease  in,  the  sugar  content  can  be  detected. 
The  quantitative  determination,  however,  is  of  diagnostic 
significance. 

Several  methods  have  been  employed  for  sugar  determi- 
nation, the  most  accurate  one  being  the  Lewis  and  Benedict 
method,  originally  described  for  blood  sugar.  The  tech- 
nic  is  as  follows:  2  c.c.  of  cerebrospinal  fluid  is  put  into  a 
25  c.c.  volumetric  flask  containing  5  c.c.  of  distilled  water, 
15  c.c.  of  saturated  picric  acid  solution  is  added,  water  filled 
up  to  25  c.c.  and  the  whole  solution  is  shaken  and  filtered. 
Eight  c.c.  of  the  filtrate  in  duplicate  are  put  into  large  Jena 
test  tubes  for  determination;  2  c.c.  saturated  picric  acid 
solution  and  1  c.c.  of  a  10  per  cent  sodium  carbonate  solu- 
tion are  added ;  the  contents  of  the  tube  is  evaporated  over 
the  flame  until  precipitation  occurs,  3  c.c.  of  Avater  is 
added  and  the  tube  heated  again  to  the  boiling  point,  in 
order  to  dissolve  the  precipitate ;  the  contents  of  the  tube  is 
now  transferred  to  a  10  c.c.  volumetric  flask,  cooled,  filled 
up  to  the  mark  with  water,  shaken  and  filtered  through  cot- 
ton into  a  colorimetric  flask;  the  color  is  compared  in  a 
Dubosque  colorimeter  either  Avith  a  dextrose  standard, 
freshly  made  up  every  time,  or  with  a  permanent  standard 
consisting  of  0.064-mg.  picramic  acid  and  0.1  gm.  sodium 
carbonate  in  1000  c.c,  and  the  results  are  calculated. 


EXAMINATION    FOR   DIAGNOSTIC    PURPOSES  159 

Epstein  described  a  rapid  microcliemical  method  for 
the  determination  of  sugar  in  the  blood  which  I  believe 
may  easily  be  applied  also  to  the  cerebrospinal  fluid.  The 
principle  is  the  same  as  that  of  the  Lewis-Benedict  method, 
except  that  a  permanent  standard  is  used  and  smaller 
quantities  of  the  fluid  to  be  tested  are  used.  It  differs  from 
the  blood  sugar  test  in  that  in  the  determination  of  sugar  in 
the  cerebrospinal  fluid,  no  sodium  fluoride  or  potassium 
oxalate  has  to  be  used  as  is  the  case  in  sugar  of  the  blood. 
The  apparatus  consists  of  the  following: 

(a)  Sahli-Gower  hemoglobinometer  stand  and  a  gradu- 
ated tube. 

(b)  Tavo  standard  color  tubes,  one  for  measuring  quanti- 
ties of  sugar  ranging  from  0.05  to  0.1  per  cent  and  the  other 
for  measuring  quantities  of  sugar  over  0.1  per  cent. 

(c)  A  test  tube  (l^  by  4  inches)  graduated  at  1.0  c.c.  and 
2.5  c.c. 

(d)  A  special  pipette  graduated  at  0.1  c.c.  and  0.2  c.c. 
(As  will  be  seen  later,  this  pipette  may  be  dispensed  with.) 

(e)  A  test  tube  suitable  for  boiling  fluid. 

The  procedure  is  as  follows:  0.2  c.c.  of  cerebrospinal 
fluid  is  drawn  up  with  the  pipette  of  the  apparatus  or  any 
other  graduated  pipette  into  the  large  graduated  test  tube. 
Distilled  water  is  then  drawn  up  into  the  pipette  and  dis- 
charged into  the  graduated  test  tube,  till  the  fluid  reaches 
the  1.0  c.c.  mark;  picric  acid  is  added  to  the  2.5  c.c.  mark, 
and  the  tube  shaken  vigorously;  the  contents  are  filtered 
through  a  small  filter,  or  centrifuged  for  2  to  3  minutes ;  1 
c.c.  of  the  filtrate  is  now  withdrawn,  put  into  the  boiling 
tube  and  heated  carefully  over  the  naked  flame.  The  con- 
tents of  the  tube  is  boiled  until  all  but  2  or  3  drops  of  the 
solution  is  evaporated.  Five-tenths  c.c.  of  a  10  per  cent 
soda  solution  is  now  added  and  the  tube  heated  again  until 
the  contents  are  down  to  a  few  drops,  the  color  of  the  fluid 
being  changed  from  yellow  to  deep  red  or  reddish  brown. 
Three  or  four  drops  of  distilled  water  are  added  and  the 


160  CEREBPiOSPI^"AL  FLUID 

tube  warmed  gently.  Tlie  contents  are  next  transferred  to 
graduated  tube  1.  The  boiling  tube  is  rinsed  several  times 
with  a  few  drops  of  water,  the  tube  being  warmed  with 
each  rinsing.  The  volume  of  the  fluid  is  then  made  up  to 
mark  50  on  the  scale.  The  color  of  the  resulting  solution 
is  now  compared  with  one  of  the  two  standard  tubes  A  or 
B.  If  the  fluid  tested  is  darker  than  the  standard  A  which 
represents  0.05  per  cent  of  sugar,  and  is  lighter  than  stand- 
ard B  which  represents  0.1  per  cent  of  sugar,  the  first 
standard  is  used  for  comparison.  The  solution  in  the 
graduated  tube  is  gradually  diluted  with  water  until  the 
color  matches.  The  percentage  of  sugar  on  using  standard 
A  is  figured  out.  Each  reading  on  scale  being  1/1000.  For 
example,  if  the  reading  is  86  then  86/1000  =  0.086  per  cent. 
If  B  is  used,  the  figure  on  the  scale  is  multiplied  by  2 
di\'ided  by  1000.     For  example,  if  the  reading  is  73,  then 

73  X  2  _  Q^^Q 
1000 

I  have  checked  the  Epstein  method  against  the  Dubosque 
colorimetric  with  a  standard  solution  of  dextrose.  The  de- 
termination by  Epstein  method  usually  gave  a  higher  read- 
ing of  dextrose  than  the  amount  originally  started  Ax-ith. 
The  percentage  of  error,  however,  was  small.  I  think  it 
could  be  accounted  for  by  the  fact  that  the  picramic  used 
by  Epstein  in  the  standard  tubes  loses  some  of  its  potency 
in  time ;  the  result  of  it  being  that  the  solutions  to  be  tested 
gave  a  higher  percentage  of  sugar  than  the  solution  really 
contained.  I  have  also  encountered  difficulty  in  using  the 
pipette  designated  by  Epstein  for  drawing  up  the  fluid. 
The  lumen  of  the  pipette  was  too  large  so  that  when  I  suc- 
ceeded in  getting  0.2  c.c.  of  cerebrospinal  fluid,  the  fluid 
would  run  out  of  the  tube  before  I  had  a  chance  to  empty  it 
into  the  test  tube.  This  difficulty,  however,  was  done  away 
Avith  by  calibrating  my  own  tubes,  using  graduated  pipettes 
and  ordinary  centrifuge  tubes  for  that  purpose,  so  that  I 
had  a  double  check  on  the  amount  used.     I  let  the  spinal 


EXAMINATION    FOR    DIAGNOSTIC    PURPOSES  161 

fluid  drop  down  into  the  centrifuge  tubes  up  to  the  0.2  c.c. 
mark  on  the  tube,  using  the  same  tube  for  the  purpose  o-f 
centrifugation. 

Chlorides 

For  the  quantitative  estimation  of  chloride  in  the  cere- 
brospinal fluid,  the  Seelman  method  originally  described 
for  the  determination  of  chloride  in  urine  is  the  most  prac- 
tical. It  requires  only  0.5  c.c.  of  fluid  and  the  results  are 
quite  accurate. 

Two  solutions  are  prepared  for  the  test.  Solution  1  con- 
sists of  the  following: 

Anhydrous,  crystallized  silver  nitrate,   (C.  P.) 29.055  gm. 

25%  nitric  acid  in  distilled  water 900.  c.c. 

Cold  saturated  solution  of  ammonioferric  ahun  in  distilled 

water    50.  " 

Distilled  water,  q.  s 100.  " 

Solution  2  consists  of: 

Ammonium  sulphocyanate 7  gm. 

Distilled  water   1000    c.c. 

Solution  2  is  intentionally  made  too  strong,  and  must  be 
standardized  by  adding  distilled  water  in  such  an  amount 
that  exactly  the  last  drop  of  2  c.c.  of  this  solution  will  bring 
about  the  end  reaction  when  added  to  1  c.c.  of  Solution  1. 
The  end  reaction  consists  of  a  reddish-brown  color,  which 
does  not  disappear  on  moderate  stirring.  If  the  second 
last  drop  produces  a  discoloration  which  disappears  rather 
slowly,  and  the  last  drop  a  deep  brown  color,  the  solution 
must  be  still  further  diluted,  until  the  discoloration  on  the 
addition  of  the  last  drop  is  a  light  reddish-brown,  which 
does  not  disappear  on  stirring  fifteen  to  twenty  seconds. 

The  test  proper  is  made  as  follows:  0.5  c.c.  of  cerebro- 
spinal fluid  to  be  tested  is  placed  in  a  porcelain  dish,  1  c.c. 
of  Solution  1  is  then  added  and  the  mixture  is  stirred  for 
about  a  minute  with  a  glass  rod.  Solution  2  is  now  added 
drop  by  drop  by  means  of  a  2  c.c.  pipette  graduated  to  at 


162  CEREBROSPINAL  FLUID 

least  .05  c.c.  and  the  inixtiii'e  is  stirr(»d  until  the  brown 
color  developing  after  each  drop  disappears.  The  amount 
of  Solution  2  which  has  been  used  to  bring  about  the  end 
reaction  is  now  read  otf,  and  the  difference  between  this 
and  2  is  equal  to  the  number  of  grams  of  sodium  chloride 
per  100  c.c.  of  the  specimen  tested.  If  for  example,  it  takes 
1.26  c.c.  of  Solution  2  to  bring  about  the  end  reaction,  the 
amount  of  chloride  in  100  c.c.  of  cerebrospinal  fluid  equals 
2.  - 1.26  which  equals  0.74  per  cent  of  chlorides. 

PHYSICOCHEMICAL  METHODS 

If  determined  accurately,  specific  gravity,  viscosity,  sur- 
face tension  and  freezing  point,  are  of  some  value  in  eluci- 
dating diagnosis  of  pathologic  conditions.  However,  since 
accurate  determinations  of  physicochemical  constants  re- 
quire a  great  deal  of  care  and  consume  a  good  deal  of  time, 
I  do  not  recommend  most  of  them  for  routine  laboratory 
use.  I  believe,  for  instance,  that  specific  gravity,  to  be  of 
any  value,  should  be  determined  by  a  pyknometer,  the  de- 
termination of  specific  gravity  by  the  urinometer  method 
being  very  inaccurate,  and  requiring  more  fluid  than  can 
be  spared  even  in  pathologic  conditions.  Tlie  i^yknoni- 
eter,  however,  is  a  delicate  instrument,  and  consumes  a 
great  deal  of  time  in  drawing  up  the  fluid  without  bubbles, 
in  weighing  the  instrument,  and  also  in  keejoing  it  at  a 
constant  temperature.  It  is,  therefore,  best  to  leave  it  out 
in  ordinary  laboratory  work. 

The  determination  of  the  H-ion  concentration  and  of  the 
alkaline  reserve  of  cerebrospinal  fluid,  however,  is  of 
greater  value  than  some  of  tlie  other  physicocliemical  con- 
stants. As  has  been  shown  in  Chapter  V  tlie  H-ion  concen- 
tration and  the  alkaline  reserve  varies  in  the  different  types 
of  meningitis  especially  after  the  fluid  stands  uncorked. 
This  makes  it  of  diagnostic  importance  to  say  nothing  of 
the  scientific  interest  attached  to  it.    I  would,  tlierefore,  ad- 


EXAMINATION    FOR    DIAGNOSTIC    PURPOSES  163 

vise  to  detormiiie  the  H-ion  concentration  and  the  alkaline 
reserve  whenever  a  sufficient  amount  oi'  cerebrospinal  fluid 
can  be  spared  after  other  more  important  tests  have  been 
made.  The  method  for  the  H-ion  concentration  in  routine 
laboratory  work,  1  would  recommend,  is  that  of  Levy- 
Rowntree-Marriott.  This  method  requires  only  3  c.c.  of 
cerebrospinal  fluid  and  very  f  ew^  apparatus.  The  gas-chain 
method,  although  more  exact,  requires  7  to  8  c.c.  of  fluid 
and  is  highly  complicated.  The  technic  of  the  Levy-Rown- 
tree-Marriott  method  is  as  follows: 

Three  c.c.  of  cerebrospinal  fluid  is  collected  directly  from 
the  lumbar  puncture  needle,  or  from  another  test  tube  into 
a  nonsol  glass  tube.  To  this  is  added  0.2  c.c.  of  the  in- 
dicator which  consists  of  a  solution  of  0.01  per  cent  of 
phenolsulphonephthalein.  The  tube  with  the  cerebrospinal 
fluid  is  now  compared  in  a  special  stand  with  one  of  the 
series  of  sealed  standards  ranging  from  a  Ph  of  6.6  to  a 
Ph  of  8.6. 

If  sufficient  fluid  has  been  obtained,  it  is  advisable  to  de- 
termine the  H-ion  concentration  immediately  after  the 
fluid  has  been  removed  from  the  body  and  also  several 
liours  later.  If  no  large  amount  of  fluid  can  be  spared,  the 
H-ion  concentration  should  be  determined  only  once,  im- 
mediately after  the  removal  of  the  fluid  from  the  body.  It 
must  always  be  kept  in  mind  that  the  H-ion  concentration 
changes  on  standing  and  the  time  factor  must  be  taken  into 
consideration  in  order  to  arrive  at  any  conclusion. 

Some  authors  have  used  a  dialyzing  tube  for  the  deter- 
mination of  the  H-ion  concentration  of  the  cerebrospinal 
fluid  by  the  indicator  method.  I  have,  however,  found 
that  with  the  exception  of  severe  cases  of  epidemic  menin- 
gitis where  the  protein  content  is  very  high,  no  dialysis  is 
necessary  and  that  the  result  obtained  by  the  indicator 
method  corresponds  quite  well  with  those  obtained  from 
the  gas-chain  method,  especially  in  Ph  reading  of  7.0  to  8.1 


164  CEREBROSPIlSrAL  FLUID 

For  the  determination  of  tlie  alkali  reserve,  the  Van 
Slyke  method  is  the  most  accurate  and  requires  the  least 
amount  of  fluid. 

Lange  Gold  Chloride  Test 

The  Lange  test  is  a  very  sensitive  one  and  is  quite 
helpful  in  detecting  various  forms  of  syphilis  of  the  nerv- 
ous system  and  often  also  in  discovering  the  type  of 
meningitis.  It  is  a  test,  however,  which  calls  for  extraordi- 
nary care  and  precision  on  the  part  of  the  one  who  is  mak- 
ing it.  To  begin  with,  the  vessels  in  which  the  solutions 
are  used  must  be  perfectly  clean.  Secondly,  the  vessels 
must  be  neutral  in  reaction.  Thus,  after  the  glassware 
has  been  cleaned  with  bichromate  solution,  for  instance, 
sufficient  water  should  be  run  through  the  vessels  to  make 
the  reaction  neutral.  The  water  used  in  making  up  this  so- 
lution must  be  doubly  distilled,  and  if  possible,  trebly  dis- 
tilled. The  pipettes  used  for  measuring  the  cerebrospinal 
fluid  and  sodium  chloride  solution  must  be  accurately  grad- 
uated. Great  care  must  also  be  taken  not  to  blow  the  pipette 
in  emptying  the  solution,  for  the  introduction  of  saliva  oi' 
carbon  dioxide  into  the  solution  will  greatly  interfere  with 
this  delicate  physicochemical  reaction.  There  is  one  point, 
however,  in  which  the  Lange  test  requires  less  precaution 
than  other  tests  and  that  is,  in  the  matter  of  the  time  inter- 
vening betAveen  the  drawing  of  the  cerebrospinal  fluid  and 
the  application  of  the  test.  AVhile  in  an  examination  for 
pellicle  or  for  the  cells  of  the  cerebrospinal  fluid  time  of 
standing  is  a  great  factor,  the  examination  with  colloidal 
gold  may  be  made,  even  after  the  cerebrospinal  fluid  has 
been  standing  for  some  time.  The  solution  for  the  test  is 
prepared  in  the  f ollow^ing  manner : 

To  1000  c.c.  of  doubly  distilled  water,  which  is  heated 
slowly  to  60°  C,  10  c.c.  of  a  1  per  cent  gold  chloride  solu- 
tion and  7  c.c.  of  a  2  per  cent  solution  of  K2CO3  are  added. 


EXAMINATIOIT   FOR   DIAGNOSTIC   PURPOSES  165 

The  mixture  is  then  rapidly  heated  to  90°  C.  The  flame  is 
then  removed  and  5  c.c.  of  a  1  per  cent  formaldehyde  solu- 
tion is  added  quickly.  The  solution  should  at  once  assume 
a  ruby  red  color.  The  solution  when  ready  for  use  should 
be  transparent,  should  be  neutral  in  reaction,  and 
should  be  precipitated  by  1.7  c.c.  of  a  1  per  cent  sodium 
chloride  solution  in  one  hour.  The  solution  usually  re- 
mains indefinitely  without  spoiling,  although  it  is  best  to 
keep  it  in  a  bottle  wrapped  in  dark  paper. 

The  technic  of  examining  cerebrospinal  fluid  for  the  col- 
loidal gold  test  is  as  follows : 

A  series  of  10  large  test  tubes  are  put  in  a  test  tube  rack 
and  numbered.  In  the  first  test  tube  0.2  c.c.  of  cerebro- 
spinal fluid  is  poured  and  to  it  is  added  1.8  c.c.  of  a  0.4  per 
cent  solution  of  sodium  chloride.  Into  each  of  the  other 
tubes,  1  c.c.  of  sodium  chloride  is  poured.  The  contents  of 
the  first  tube  are  then  thoroughly  mixed  and  1  c.c.  of  the 
amount  is  poured  into  the  second  tube.  The  contents  of 
the  second  tube  are  then  mixed  and  1  c.c.  of  its  solution 
is  emptied  into  the  third  tube.  And  so  the  processes  con- 
tinue with  all  the  tubes,  until  1  c.c.  of  the  solution  in  the 
ninth  tube  has  been  emptied  into  the  tenth  tube.  The  solu- 
tion in  the  tenth  tube  is  then  thoroughly  mixed  and  1  c.c. 
of  its  contents  is  removed  and  discarded.  This  leaves  each 
tube  with  a  content  of  1  c.c.  and  gives  the  following  series 
of  dilution  1 :10, 1 :20, 1 :40, 1 :80, 1 :160, 1 :320, 1 :640 ;  1 :1280 ; 
1:2560, 1:5120.  Five  c.c.  of  the  prepared  colloidal  gold  solu- 
tion is  then  adde<i  to  each  test  tube  and  the  tubes  are  put 
away  and  the  changes  taking  place  in  them  observed.  Gen- 
erally some  change  occurs  in  a  very  short  time,  but  it  is 
best  not  to  attempt  to  judge  the  reaction  before  the  lapse  of 
an  hour  and  it  is  still  better  to  wait  until  the  next  day,  for 
sometimes  it  takes  24  hours  for  a  completion  of  the  reaction. 
The  tubes  should  be  read  in  daylight  as  artificial  light  may 
cause  a  false  interpretation  of  the  changes. 


166  CEREBROSPINAL  FLUID 

Mastic  Test 

The  mastic  test  which  has  been  described  by  Emanuel 
has  been  used  by  some  observers  with  success  and 
those  observers  recommend  it  for  use  in  routine  exami- 
nation of  cerebrospinal  fluid.  The  principle  is  tlie  same 
as  that  of  the  Lange  gold  chloride  and  the  advantage, 
claimed  for  this  test  is  the  fact  that  the  mastic  solution 
is  easily  made  up,  much  more  easily  than  the  gold  chloride 
solution.  Until  we  get  further  data  on  the  subject,  I  would 
suggest  that  between  the  two  tests,  the  Lange  and  the  mas- 
tic, the  first  is  preferable.  However,  when  time  permits, 
the  mastic  test  should  be  employed  for  corroborative  evi- 
dence. The  technic  described  for  the  mastic  test  is  that  of 
ICmanuel  modified  by  Cutting.     The  technic  follows: 

A  stock  mastic  solution  is  made  by  dissolving  10  gm. 
of  gum  mastic  in  100  c.c.  of  absolute  alcohol.  The  solution 
is  filtered.  This  stock  solution  keeps  indefinitely  if  well 
corked.  To  2  c.c.  of  this  solution  18  c.c.  of  absolute  alcohol 
are  added,  and  insufflated  rapidly  into  80  c.c.  of  distilled 
water,  this  makes  an  emulsion  of  mastic  which  is  opales- 
cent when  held  to  the  light.  This  solution  can  be  used  im- 
mediately or  after  several  days;  indeed,  the  reactions  seem 
to  be  more  easily  read  when  a  solution  is  employed  which 
has  stood  for  at  least  a  few  hours. 

Next,  a  1.25  per  cent  sodium  chloride  solution  is  made 
with  distilled  water,  and  to  each  99  c.c.  of  this  salt  solu- 
tion is  added  1  c.c.  of  a  0.5  per  cent  solution  of  potassium 
carbonate  made  up  with  distilled  water. 

Then  six  small  test  tubes  are  placed  in  a  rack.  These 
tubes  should  have  been  w^ashed  thoroughly  in  tap  water, 
then  in  denatured  alcohol,  to  remove  any  old  mastic  adher- 
ing to  the  sides  of  the  tubes,  rinsed  in  distilled  water  and 
dried,  conveniently  in  the  hot  air  oven.  To  the  first  tube 
1.5  c.c.  of  the  coml)ined  salt  and  potassium  carbonate  so- 
lutions are  added,  and  to  the  others  1  c.c.  each.  Then  0.55 
c.c.  of  spinal  fluid  is  added  to  the  first  and  after  thorough 


EXAMINATION    FOR    DIAGNOSTIC    PURPOSES  167 

mixing,  1  c.c.  is  transferred  from  the  first  to  the  second, 
1  c.c.  from  the  second  to  the  tliird,  and  so  on,  the  last  cubic 
centimeter  that  remains  over  from  the  next  to  the  last  tube 
being  tlirown  out,  and  no  spinal  fluid  being  put  in  the  con- 
trol. Now  to  each  tube,  1  c.c.  of  tlie  mastic  solution  is 
added  and  stirred  thoroughly  with  a  glass  rod,  care  being 
taken  to  wash  the  rod  with  distilled  water  before  going  to 
the  next  series.  It  is  best  to  finish  each  group  before  be- 
ginning another. 

The  racks  are  set  away,  and  in  from  twelve  to  twenty- 
four  hours  the  end  results  can  be  read.  If  the  racks  are 
placed  in  an  incubator  at  37.5°  C,  the  precipitation  is  com- 
plete in  from  six  to  twelve  hours. 

CYTOLOGIC  EXAMINATION 

The  examination  of  the  cells  in  the  cerebrospinal  fluid 
is  of  extreme  importance  diagnostically  and  should  be  in- 
cluded in  every  routine  examination  of  the  fluid.  There 
are  essentially  two  methods  of  counting  the  cells;  one  is  the 
sedimentation,  or  French  method,  and  the  other  is  the 
counting  chamber  method. 

The  French  Method  of  Cell  Counting 

This  method,  originally  described  by  Ravant,  Sicard  and 
Widal,  is  as  follows:  3  to  4  c.c.  of  fluid  is  centrifuged  for 
forty-five  minutes.  The  fluid  is  then  poured  off  and  a  few 
drops  of  the  sediment  are  drawn  up  into  a  pipette  of  small 
caliber,  and  put  on  a  glass  slide,  making  a  smear  of  uni- 
form thickness.  The  slide  is  dried  in  the  air,  fixed  in  the 
flame,  and  stained  with  methyl  ])lue  or  with  Wright  stain 
and  examined  under  the  microscope  with  the  high  power 
or  oil  immersion  lens.  The  number  in  each  field  is  now 
read.  The  results  of  this  examination  are  recorded  as 
follows: 

0-3  cells  per  field — normal 

4-6  cells  per  ficltl — suspicious 

7-20  cells  per  field— abnormal 

20-150  cells  per  field — markedly  pathologic 


168 


CEREBROSPIlSrAL  FLUID 


Chamber  Method  of  Cell  Counting 

Either  a  special  counting  chani))er  for  spinal  fluid,  such 
as  the  Fuchs-Rosenthal  counting  chamber,  or  the  ordinary 
leucocyte  chamber,  such  as  the  Thoma-Zeiss  or  Neubauer 
chamber  may  be  used. 

The  Fuchs-Rosenthal  chamber  (Fig.  33)  is  larger  than 
the  ordinary  leucocyte  chamber,  being  16  mm.  square  and 
0.2  mm.  deep,  whereas  the  Thoma-Zeiss  chamber  is  only  1 
mm.  square  and  0.1  mm.  deep.     (Fig.  34.) 

The  cells  are  counted  in  the  following  way  }»y  the  Fuchs- 
Rosenthal  method :  the  fluid  is  drawn  up  into  a  white  blood 
pipette  to  mark  1.0  and  then  the  staining  fluid,  consisting 


mnnnannmaivi 


■■■■  ■■■■  ■BBH  HUB 
■■■■ ■■■■ ■■■■ ■« — 


I  ■■■■ ■■■■ ■■■■ ■■■■ 

■■■■■■■■ ■■■■ ■■■■ 


Fig.      33. — i'uciis-Kosenthal      chamber 
for  counting  cells  in  cerebrospinal  fluid. 


Fig.  34. — -Xeubauer  blood  counting 
chamber  which  may  be  used  for  cere- 
brospinal  fluid. 


of  methyl  violet  0.2  gm.,  glacial  acetic  5  c.c.  and  water  to  100 
c.c.  is  drawn  up  to  mark  11.  The  resulting  number  gives 
the  cells  contained  in  ^%  mm.  The  Fuchs-Rosenthal  cham- 
ber also  allows  the  differentiation  of  the  different  types  of 
cells  present  in  the  fluid. 

In  using  an  ordinafy  blood  counting  chamber  for  count- 
ing the  cells  in  cerebrospinal  fluid  any  of  the  standard 
chambers  answer  the  purpose  quite  well.  The  same  solu- 
tion used  for  staining  the  cells  in  the  Fuchs-Rosenthal 
chamber  is  also  used  here,  namely,  methyl  violet  0.2  gm., 
glacial  acetic  5  c.c.  and  water  to  100  c.c.  The  methyl  violet 
is  drawn  up  into  the  pipette  to  mark  1.0  and  the  spinal  fluid 


EXAMINATION    FOR   DIAGNOSTIC   PURPOSES  169 

to  mark  11.  This  gives  a  dilution  of  1 :10.  Since  the  ruled 
surface  of  the  blood  counting  chamber  has  an  area  of  9 
square  millimeters  and  the  depth  of  the  chamber  is  Ho  milli- 
meter, the  total  count  of  the  ruled  surface  will  be  the  amount 
contained  in  the  entire  volume  which  is  %o  cubic  millimeters.. 
To  obtain  the  number  of  cells  in  one  cubic  millimeter  %  of 
the  entire  cell  count  has  to  be  added  to  the  number  found. 
Since  to  ten  parts  of  the  spinal  fluid,  one  part  of  counting 
fluid  was  added  the  result  obtained  corresponds  to  %o  of 
the  number  of  cells  in  a  cubic  millimeter  of  pure  spinal 
fluid.  Therefore,  in  order  to  obtain  the  number  of  cells 
in  one  c.nun.  of  spinal  fluid,  we  have  to  make  allowance 
for  this  by  adding  %  to  the  result  obtained.  This  gives 
the  number  of  cells  per  cubic  millimeter  of  undiluted  cere- 
brospinal fluid. 

Example:  Let  us  suppose  that  the  chamber  contains  90  cells  in  its  nine 
fields. 

A  counting  chamber  %q  c.mm.  volume  contains  90  cells. 

Then  Ic.mm.  will  contain  199  x  90  cells  =  100  cells. 

In  other  words,  100  cells  are  contained  in  one  cubic  millimeter  of  space 
which  contains  nine  parts  of  spinal  fluid  and  one  part  of  methyl  violet?.  In 
ten  parts  of  fluid,  therefore,  we  will  have  111  cells. 

Comparative  Value  of  the  Two  Methods 

The  centrifuge  method  of  counting  the  number  of  cells 
in  the  spinal  fluid  is  open  to  several  rather  serious  objec- 
tions. First  of  all  the  method  is  not  accurate  enough  as  it 
is  not  always  easy  to  measure  the  exact  amount  of  fluid 
put  into  the  centrifuge  tube.  Moreover,  the  size  of  the  drop 
taken  from  the  sediment  of  the  fluid  can  not  possibly  be 
the  same  at  all  times.  Furthermore,  the  force  of  centrifu- 
gation  and  the  rate  of  velocity  of  the  centrifuge  are  im- 
portant determining  factors.  Still  another  drawback  is 
the  fact  that  the  centrifuge  method  requires  a  great  amount 
of  fluid  for  counting,  more  than  can  usually  be  spared. 
For  precise  results,  I  should  therefore,  recommend  the 
use  of  the  blood  or  fluid  counting  cliamber.  However,  when 
a  rough  estimate  of  the  number  of  cells  is  all  that  is  re- 


170  CEREBROSPIXAL  FLUID 

quired,  the  centrifuge  method  is  perhaps  the  more  con- 
venient one  to  use.  Anotlier  point  in  its  favor  is  the  fact 
that  it  enables  one  to  study  the  type  of  the  cell  on  one  and 
the  same  slide. 

There  is  one  thing-,  however,  that  can  not  l)e  emphasized 
too  strongly  and  that  is,  that  whatever  method  is  em- 
ployed, the  examiner  should  thoroughly  familiarize  him- 
self with  it  and  should  use  it  as  a  standard,  so  that  he  can 
easily  detect  even  a  slight  increase  in  the  cells  of  the  spinal 
fluid.  Another  thing  to  remember  is  that  the  cells  should 
be  counted  immediately  after  withdrawal  of  the  fluid  from 
the  body,  as  they  undergo  autolysis  upon  standing. 

When  the  cerebrospinal  fluid  is  blood  stained,  the  speci- 
men may  still  be  utilized  for  cell  counting,  if  only  a  rough 
count  is  desired.  It  is  known  that  under  normal  conditions 
the  blood  contains  one  lymphocyte  to  three  leucocytes.  To 
obtain  the  number  of  lymphocytes,  therefore,  the  white 
blood  cells  in  the  spinal  fluid  should  be  counted  and  the  re- 
sult divided  by  three. 

Type  of  Cells 

In  doing  a  differential  cell  count,  care  must  be  taken  to 
count  only  the  white  cells  and  not  the  red  cells  or  the  de- 
bris. When  the  fluid  is  turbid  as  in  epidemic  or  in  pneumo- 
coccus  meningitis,  a  differential  cell  count  may  be  made 
on  the  fluid  directly  without  centrifugation.  As  a  rule, 
however,  it  is  best  to  centrifuge  the  fluid  from  fifteen  to 
thirty  minutes  through  about  1500  revolutions.  If  the 
fluid  contains  only  a  very  small  amount  of  protein, 
some  egg  albumin  may  be  rubbed  on  the  slide  to  prevent 
the  smear  from  being  washed  off.  The  fluid  may  be  stained 
with  Wright's  stain,  or  with  other  blood  stains  such  as 
Jenner's,  Leischman's,  or  eosin  hematoxylin  and  the  cells 
counted  according  to  their  type  and  the  cell  count  ex- 
ju'essed  in  percentages.  As  a  rule,  however,  no  special 
stain  is  needed  for   tlie   differential   cell   count,   for   usii- 


EXAMINATION    FOR   DIAGNOSTIC    PijRPOSES         '  171 

ally  the  ^ram  stain  shows  the  cells  quite  well  and  also 
stains  the  organisms  at  the  same  time.  If  tuberculous 
meningitis  is  suspected,  the  special  carbol  fuchsin  stain 
should  be  used,  as  it  shows  the  tubercle  bacilli  and  also 
stains  the  cells  well. 

BACTERIOLOGIC 

One  must  be  very  careful  in  doing  bacteriologic  work  on 
spinal  fluid,  for  there  are  many  technical  factors  that  may 
interfere  with  the  success  of  the  work.  Such  factors  may 
be  wrong  media,  insufficient  length  of  time  for  the  or- 
ganism to  develop,  contamination  of  the  media,  dirty  slide, 
overheating  of  the  slide,  (protein  particles  often  look  like 
bacteria)  and  faulty  stains.  At  times,  I  have  found  or- 
ganisms in  a  spinal  fluid  smear  done  by  a  novice  that  did 
not  belong  to  the  spinal  fluid,  but  were  introduced  while  in 
the  centrifuge  tube,  or  were  on  the  slide  used  for  a  urine 
examination. 

Culture  Media 

One  drop  on  a  platinum  needle  or  several  drops  are 
planted  on  a  culture  medium.  The  kind  of  media  to  plant 
the  spinal  fluid  on  depends  on  the  type  of  organism  looked 
for.  Most  organisms  grow  on  plain  agar.  Meningococci 
have  given  some  workers  great  difficulty  in  that  they  do 
not  grow  easily  on  ordinary  media.  I,  however,  have 
grown  meningococci  successfully  on  ascitic  dextrose  agar 
and  also  sheep  blood  agar.  It  is  strongly  advisable  to  im- 
plant every  specimen  of  cerebrospinal  fluid  on  several  me- 
dia, such  as  blood  agar,  ascitic  dextrose  agar,  and  glucose 
and  agar.  The  culture  should  be  examined  microscopically 
after  twenty-four  hours'  incubation,  and  also  after  forty- 
eight  hours,  as  some  organisms  do  not  manifest  their  char- 
acteristics till  after  forty-eight  hours  of  incubation. 

In  addition  to  the  culture  media,  it  is  a  good  plan  to 
put  the  spinal  fluid  left  over  in  the  test  tube  directly  into 


172  CEKEBROSPIXAL  FLUID 

the  incubator  and  to  examine  it  twelve  to  twenty-four 
hours  later  for  organisms,  as  it  has  been  found  that  some 
organisms,  especially  the  meningococci,  will  show  up  well 
after  the  spinal  fluid  has  been  incubated  for  several  hours. 

Direct  Smear 

Several  cubic  centimeters  of  spinal  fluid  are  centrifuged 
in  a  centrifuge  tube  for  several  minutes,  the  supernatent 
fluid  is  poured  off  and  the  sediment  is  put  on  a  slide  and 
stained.  Where  suppurative  organisms  are  suspected  it  is 
best  to  stain  with  both  methyl  blue  and  gram  stain.  When 
tubercle  bacilli  are  searched  for,  the  fluid  should  be  al- 
lowed to  centrifuge  at  high  speed  for  forty-five  minutes 
to  one  hour  and  stained  by  the  Ziehl-Neelsen  method.  If 
there  is  more  than  one  tube  of  cerebrospinal  fluid,  it  is  ad- 
visable to  examine  the  pellicle  formed  in  the  tube  for  tu- 
bercle bacilli.  In  mj-  hands  this  has  given  good  results. 
If  the  spinal  fluid  is  very  thick,  the  smear  may  be  taken 
from  the  uncentrifuged  spinal  fluid. 

IMMUNOLOGIC 

Among  the  immunologic  tests  in  routine  cerebrospinal 
fluid  examinations  are  agglutination  tests  for  meningococci 
and  pneumococci,  precipitin  tests  of  cerebrospinal  fluid 
with  antimeningococcus  serum,  the  neutralization  test  for 
anterior  poliomyelitis,  and  the  AVassermann  test.  Two  ag- 
glutination tests  have  been  described  for  the  meningococ- 
cus; the  macroscopic  and  the  microscopic. 

Macroscopic  Method 

A  polyvalent  antimeningococcus  serum  which  has  been 
proved  by  appropriate  tests  to  agglutinate  established 
strains  of  meningococcus  in  dilutions  from  1 :200  to  1 :2000 
is  used. 


EXAMINATION    FOR    DIAGNOSTIC    PURPOSES 


173 


A  meningococcus  culture,  preferably  only  24  hours  old, 
grown  on  ascitic  dextrose  agar  or  on  blood  agar  is  washed 
down  with  2  or  3  c.c.  of  an  0.8  per  cent  sterile  salt  solution ; 
0.2  c.c.  of  this  meningococcus  emulsion  is  added  to  a  series 
of  small  test  tubes  each  one  containing  0.8  c.c.  of  various 
serum  dilutions  such  as  1:10,  1:20,  1:40,  1:80,  1:100,  1:500, 
1:1000,  1:2000  strength.  This  is  mixed  and  incubated  over- 
night (15  to  20  hours)  at  56°  C.    Controls  of  meningococcus 


B. 


c. 


D. 


B. 


Fig.   35. — Photograph   showing   agglutination   of   meningococci  by   the   macroscopic  method, 
A.   IJmulsion    of   meningococci  +  1 :10   dilution    of   antimeningococcus    serum. 
O.   Control   of   emulsion  of  meningococci  +  salt  solution. 

C.  Emulsion    of    meningococci  +  1:160    dilution    of   antimeningococcus   serum. 

D.  Control. 

K.   Kmulsioti    of    meningococci  +  1 :640    dilution    of    antimeningococcus    serum. 
F.  Control. 


emulsion  added  to  0.8  c.c.  of  salt  solution  are  also  incu- 
bated. If  the  culture  in  question  is  meningococcus,  a  floc- 
culent  precipitate  will  be  seen  in  the  tubes  containing  the 
bacterial  emulsion  and  antimeningococcus  serum,  the  heavi- 
ness of  the  precipitate  depending  on  the  amount  of  dilution. 
The  controls  will  be  free  from  precipitate.    A  true  menin- 


174 


CEREBROSPINAL  FLUID 


A.  Agglutination    by   specific    serum. 


/« 


\ 


B.   Absence    of   agglutination    with    normal   horse   serum. 
Fig.    36. — Microscopic    method    of    agglutinating    meningococci.      (TunniclifF.) 


teXAMINATIOlSf    FOR    DIAGNOSTIC    PURPOSES 


175 


^oeocciis  is  completely  a^-^lutinated  in  1 :200  dilution  of 
polyvalent  serum.  It  is  usually  also  agglutinated  in  higher 
dilutions  ♦(Fig.  35).  The  other  gram-negative  cocci  are  usu- 
ally not  agglutinated  at  all  and  never  in  greater  dilutions 
than  1 :1()0.  Micrococcus  flavus  sometimes  agglutinates  in 
polyvalent  and  monovalent  meningococcus  serum  in  1 :50  di- 
lutions but  may  be  differentiated  from  the  meningococcus 
by  its  cultural  properties. 


I'"ig.     37. — Agglutination     of    meningococci    by     the    microscopic     method. 

800  diameters.) 


(Magniticatioii 


Microscopic  Method 

A  more  rapid  method  than  the  macroscopic  for  the  ag- 
glutination of  meningococci  has  been  described  by  Tunni- 
cliff.  Ecjual  parts  of  antinieningococcus  serum,  whole  hu- 
man blood  in  sodium  citrate  solution  (one  part  of  blood  to 
2  per  cent  sodium  citrate  in  salt  solution),  and  a  suspension 
of  organisms  are  incubated  for  ten  minutes  and  then 
stained  and  examined.  Normal  horse  serum  with  a  sus- 
pension of  organisms  is  used  as  control.  In  the  mixture 
with  normal  horse  serum  there  is  very  little  or  no  clump- 


176  CEREBROSPINAL  FLUID 

ing  of  the  mening;ococcus,  wliile  in  the  mixture  containing 
antimeningococcus  serum  there  is  decided  agghitination 
(Figs.  36  and  37).  The  suspension  of  the  organisms  is 
made  by  adding  one  or  two  colonies  of  the  original  culture 
to  two  or  three  drops  of  salt  solution.  One  drop  of  serum  is 
drawn  up  in  a  bent  capillary  tube,  and  the  upper  point 
marked,  then  an  equal  amount  of  citrated  blood  and  later 
the  suspension  of  the  organisms  are  drawn  up.  The  con- 
tent of  the  pipette  is  now  carefully  mixed  and  heated  for  ten 
minutes  at  36°  C,  or  left  at  room  temperature  for  twenty 
minutes;  after  incubation  the  content  is  blo\^^l  out  on  a 
glass  slide,  spread  with  cigarette  paper  and  stained  unfixed 
with  carbol  thionin  or  fixed  with  heat  and  stained  with 
methylene  blue. 

Either  of  the  agglutination  tests  gives  good  results.  I 
would  advise  that  whenever  possible  both  the  macroscopic 
and  microscopic  agglutination  should  be  carried  out;  when 
the  time  is  limited  the  microscopic  method  can  be  depended 
upon. 

Agglutination  of  pneumococci  is  utilized  to  determine 
the  type  of  the  organism,  Type  I,  Type  II  and  Type  III,  an- 
tipneumocoecus  serum  being  used  for  that  purpose. 

Precipitation  of  Cerebrospinal  Fluid  with  Antimeningo- 
coccus Serum 

According  to  Vincent  and  Ballot  normal  cerebrospinal 
fluid  does  not  form  any  precipitate  with  antimeningococcus 
serum,  while  fluid  from  meningococcus  meningitis  is  pre- 
cipitated, when  incubated  with  antimeningococcus  serum. 

The  teclmic  of  the  test  is  as  follows:  The  spinal  fluid  is 
centrifuged  till  it  becomes  clear.  Two  to  five  drops  of  anti- 
meningococcus serum  are  then  added  to  50  and  100  drops  of 
the  clear  spinal  fluid.  The  specimens  are  incubated  at  50° 
C.  for  eight  to  fourteen  hours.  If  the  fluid  is  one  of  me- 
ningococcus meningitis,  the  mixture  becomes  turbid.  A  tube 


EXAMINATION    FOR    DIAGNOSTIC    PURPOSES  177 

contain in^i^'  spinal  fluid  to  which  no  antimeningococcus  se- 
rum has  been  added  is  used  as  a  control. 

While  other  workers  have  confirmed  the  observation  of 
Vincent  and  Ballot,  it  has  been  pointed  out  that  at  times 
fluids  from  other  types  of  meningitis  will  show  the  same 
reaction  with  antimeningococcus  serum.  One  of  the  diffi- 
culties of  the  test  is  that  often  it  is  impossible  to  clarify 
the  spinal  fluid  of  meningococcus  meningitis  even  after  cen- 
trifugation  for  a  long  period.  This  test  should  therefore  be 
performed  only  when  there  is  sufficient  fluid  left  over  from 
other  more  necessary  tests. 

Guinea  Pig  Inoculation 

It  is  often  necessary  to  employ  the  inoculation  test  to  de- 
cide wiiether  or  not  the  process  is  tuberculous  in  nature. 

Five  to  10  c.c.  of  cerebrospinal  fluid  is  injected  into  the 
groin  of  a  guinea  pig.  A  month  later  0.1  mg.  of  Old  Tuber- 
culin is  injected  into  the  axilla  of  the  pig.  If  the  meningitis 
is  tuberculous  in  nature  the  pig  usually  dies  the  morning 
after  the  injection  of  the  tuberculin.  Tubercles  are  found 
postmortem  in  both  the  spleen  and  the  inguinal  glands. 

Neutralization  Test 

Some  authors  employ  the  neutralization  test  in  polio- 
myelitis. The  technic  of  this  test  is  as  follows:  A  fatal 
dose  of  active  virus  is  mixed  with  the  suspected  fluid  ob- 
tained during  the  stage  of  recovery.  This  mixture  is  in- 
cubated and  injected  intracerebrally  into  a  monkey.  Fail- 
ure of  the  disease  to  develop  in  the  monkey  indicates  neu- 
tralization of  the  virus. 

The  Wassermann  Reaction 

It  is  impossible  to  describe  all  the  details  of  the  Wasser- 
mann reaction  in  a  small  volume.  I  shall  therefore,  limit 
myself   here   to   only   those   factors   in   the   Wassermann 


178  CEREBROSPINAL  FLUIIJ 

reaction  tliat  have  a  special  bearing  on  the  subject  of  cere- 
brospinal fluid. 

Principle. — The  blood  serum  and  cerebrospinal  fluid  of 
persons  affected  with  syphilis  contains  syphilitic  anti- 
bodies. The  presence  or  absence  of  syphilitic  antibodies 
in  the  system  is  demonstrated  by  the  complement-fixation 
test,  or  the  Wassermann  test  as  it  is  more  connnonly  known. 
The  substances  necessarj^  for  complement  fixation  are: 
antigen,  fluid  to  be  tested,  and  complement.  An  antigen  is 
a  substance  which,  when  injected  into  an  animal,  causes  the 
organism  to  react  ])y  the  formation  of  antil)ody.  The  fluid 
to  be  tested  supplies,  if  positive,  the  syphilitic  antibody. 
Complement  is  a  substance  present  in  fresh  blood  serum 
which  is  necessary  for  the  binding  of  antigen  to  anti- 
body. The  AVassermann  reaction  is  called  a  complement- 
fixation  test  although  it  is  not  really  a  complement  fixation 
in  the  strictest  sense  of  the  term  unless  a  suspension  of 
spirochetes  is  used  as  an  antigen. 

Different  kinds  of  antigen  are  used  for  the  AVassermann 
test,  (a)  an  aqueous  extract  of  syphilitic  liver  (original 
method);  (b)  an  alcoholic  extract  of  syphilitic  liver;  (c) 
an  alcoholic  extract  of  normal  liver;  (d)  an  alcoholic  ex- 
tract of  heart  (either  human  or  beef)  reinforced  with  cho- 
lesterin;  (e)  ether  soluble,  acetone  insoluble  extract  of 
heart.  At  present  alcoholic  extracts  of  heart  are  generally 
used  as  antigen. 

The  complement  consists  of  blood  serum  of  healthy 
guinea  pigs  diluted  with  sterile  normal  salt  solution. 

The  amboceptor  (antisheep  antibody)  is  contained  in 
the  serum  of  rabbits  inununized  with  washed  sheep  cor- 
puscles. 

If  the  cerebrospinal  fluid  contains  syjjhilitic  antibodies, 
the  antigen  combines  with  the  syjihilitic  antil)ody  and  the 
complement,  so  that  when  antisheep  amboceptor  and  sheep 
cells  are  added,  the  complement  is  already  bound  and  tliere- 


EXAMINATION    FOR   DIAGNOSTIC   PURPOSES  179 

foro  hemolysis  can  not  take  place.  If  there  are  no 
syphilitic  antibodies  in  the  fluid,  the  complement  unites 
with  the  antisheep  antibody  or  amboceptor  and  the  sheep 
corpuscles  and  produces  hemolysis.  Table  XXXVIII  shows 
the  process  in  the  Wassermann  reaction  of  both  syphilitic 
and  nonsyphilitic  cases. 

Table  XXXVIII 


POSITIVE 

NEGATIVE 

I.  Antigen 

I.  Antigen 

+ 

Syphilitic  Antibody 

+ 

Complement 

II.  Antibody  or  Antisheep 

II.  Complement 

Amboceptor 

+ 

+ 

Antibody  or  Antisheep 

Sheep  Corpuscles 

Amboceptor 

+ 

Sheep  Corpuscles 

The  amount  of  fluid  used  for  the  Wassermann  test  is  not 
always  the  same.  Some  use  as  little  as  0.2  c.c.  of  fluid, 
wdiereas  others,  notably  Thomson,  use  as  much  as  1.0  and 
even  1.2  c.c.  It  has  been  found  that  the  small  amounts  do 
not  give  positive  results  as  frequently  as  the  larger.  This 
fact,  I  believe,  explains  the  great  number  of  negative  Was- 
sermann reactions  on  cerebrospinal  fluid  by  the  older 
authors  who  used  very  small  amounts  for  the  tests.  On  the 
other  hand,  large  amounts  of  cerebrospinal  fluid  such  as 
Thomson  advises  are  likely  to  be  anticomplementary. 
Schottmiiller 's  suggestion  that  various  amounts  of  the  fluid 
be  used  for  the  same  test,  is,  I  believe  the  most  commend- 
able plan. 

Schottmiiller  advises  the  use  of  a  series  of  Wassermann 
tests  with  fluid  varying  in  amount  fi'om  0.2  to  1  c.c.  and 
with  dilutions  of  salt  solution. 


180 


CEREBROSPINAL  FLUID 


Table  XXXIX 


TUBE   1 

TUBE   2 

TUBE    3 

TUBE   4 

TUBE   5 

c.c. 

C.C. 

C.C. 

C.C. 

C.C. 

Cerebrospinal  Fluid 

0.2 

0.4 

0.6 

0.8 

1.0 

NaCl  Solution 

0.8 

0.6 

0.4 

0.2 

Antigen 

1.0 

1.0 

1.0 

1.0 

1.0 

Complement 

1.0 

1.0 

1.0 

1.0 

1.0 

Amboceptor  plus  corpuscles  2.0 

2.0 

2.0 

2.0 

2.0 

It  is  advisable  to  carry  the  amounts  of  cerebrospinal 
fluid  even  further  than  is  indicated  in  Table  XXXIX.  It  is 
best  to  make  the  Wassermann  test  with  freshly  drawn  cere- 
brospinal fluid.  If  the  test  can  not  be  made  immediately 
after  the  withdrawal  of  fluid,  it  should  be  put  away  in  the 
ice  box  without  preservative.     The  cerebrospinal  fluid  is 


Table  XL 
Examination  of  Cerebrospinal  Fluid  for  Diagnostic  Purposes 


/ 

Very  Iviportant 

Immediate  Examination 

For                    Examination  after  24  liours 

Amount 

Presence  or  absence  of  pellicle 

Color 

Foam 

Measurement  of  sulphosalicylic  and 

Cell  Count 

mercuric  chloride  sediment. 

Differential  Count 

Cultures 

Examination  of  cultures 

Direct  Smear 

Noguchi 

Agglutination 

Koss-Jones 

Sulphosalicylic 

< 

Mercuric  Chloride 

Lange 

Wassermann 

Chlorides 

II 

Less  Important 

Permanganate 

index 

Sugar 

H-ion  Concentration 

Alkali  Keserve 

Cataphoresis 

Mastic  Test 

EXAMINATION   FOR   DIAGNOSTIC   PURPOSES  181 

not  inactivated.  Preliminary  titrations  must  be  made  on 
antigen,  complement  and  amboceptor  before  the  test  is  set 
up.  The  proper  dose  of  antigen  I  believe  to  be  one-fourth 
of  anticomplementary  unit  and  the  proper  dose  of  comple- 
ment and  amboceptor  to  be  two  units  each.  Control  tubes 
of  the  cerebrospinal  fluid  should  be  set  up  with  the  test. 

The  cerebrospinal  fluid,  salt  solution,  antigen  and  com- 
plement are  incubated  for  one  hour  at  37.5°  C.  Then  the 
antisheep  amboceptor  and  the  siieep  corpuscles  are  added 
and  the  solution  is  returned  to  the  incubator  where  it  is 
allowed  to  remain  from  30  minutes  to  2  hours.  At  the  ex- 
piration of  this  time,  it  is  taken  out  and  examined.  If 
hemolysis  is  present  the  test  is  negative ;  if  there  is  an  inhi- 
bition of  hemolysis,  the  test  is  positive. 

Bibliography 

Alzheimer:  Einige  Methoden  zur  Fixierung  der  zelligen  Elemente  der  Cere- 
brospinalfliissigkeit,   Centralbl.   f.   Nervenh.   u.   Psychiat.,   1907,  xxx,   449. 

Andernach :  Beitrage  zur  Unteisuchung  des  Liquor  cerebrospinalis  mit  be- 
sonderer  Beinicksichtigung  der  zelligen  Elemente,  Arch.  f.  Psyehiat.,  1910, 
xlvii,  806. 

Black,  Rosenberg  and  McBride:  The  Colloidal  Gold  Test,  Jour.  Am.  Med. 
Assn.,  1917,  Ixix,  1855. 

Dlumenthal:      Serodiagnose   der   Syphilis,  Dermat.   Ztschr.,   1910,  xvii,   1. 

Boveri:  Di  una  nuova  reazione  del  liquido  cefalo  rachidano,  Riv.  di  patol. 
nerv.,  1914,  xix,  280, 

Cutting:  A  New  Mastic  Test  for  the  Spinal  Fluid,  Jour.  Am.  Med.  Assn., 
1917,  Ixviii,  1810. 

Emanuel:  Eine  neue  Reaktion  zur  Untersuchung  des  Liquor  Cerebrospinalis, 
Berl.  klin.  Wchnschr.,  1915.,  lii,  792. 

Epstein:  An  Accurate  Mieroeheinical  Method  of  Estimating  Sugar  in  the 
Blood,  Jour.  Am.  Med.  Assn.,  1914,  xiii,  1667. 

Fuchs  and  Rosenthal:  Physikalische,  chemische  u.  anderwertige  Untersuch- 
ungen  der  Cerebrospinalflussigkeit,  Wiener,  med.  Presse,  1904,  xlvii, 
44. 

Grulee  and  Moody:  Lange's  Colloidal  Gold  Chlorid  Test  on  the  Cerebro- 
spinal Fluid  in  Congenital  Syphilis,  Jour.  Am.  Med.  Assn.,  1913,  Ixi,  13. 

Lajige:  Die  Ausflockung  koUoidalen  Goldes  durch  Zerebrospinalfliissigkeit 
bei  luetischen  Affektionen  des  Zcntralnervensystems,  Ztschr.  f.  Chemo- 
therap.,  1913,  i,  44. 

Lowrey:     Cerebrospinal  Fluid  Tests,  Especially  the  Gold  Reaction  in  Psychi- 
atric Diagnosis,  Jour.  Nerv.  and  Mcnt.  Dis.,  1917,  xlvi,  186. 
The  Mastiche  and  Potassium  Permanganate  Tests  Applied  to  the  Cerebro- 
spinal Fluid  of  the  Insane,  Boston  Med.  and  Surg.  Jour.,   1917,  clxxvii, 
115. 

Mann  and  van  Saun:  Value  of  Chemical  Tests  on  the  Serums  and  Spinal 
Fluids  of  Syphilitics,  New  York  Med.  Jour.,  1918,  cvii,  783. 


182  CEREBROSPINAL  FLUID 

Miller,   Brush,   Hammers  and   Felton :      A   Further   Study   of   the   Dias:nostic 

Value  of  the  Colloidal  Gold  Reaction,  Together  with  a  Method  for  the 

Preparation  of  the  Reagent,  Bull.  Johns  Hopkins  Hosp.,  1915,  xxvi,  391. 
Noguchi :     The   Relation   of   Protein,   Lipoids   and   Salts   to   the   Wassermann 

Reaction,  Jour.  Exper.  Med.,  1909,  xi,  84. 
Eine  fiir  die  Pi-axis  geeignete  leicht  ausfiihrbare  Methode  der  Serumdiag- 

nose  l>ei  Syphilis,  Miinchen.  med.  Wchnschr.,  1909,  Ivi,  494. 
Serum  Diagnosis  of  SA-philis,  J.  B.  Lippiucott  Co.,  1910. 
Nonne:     Weitere  Erfahrungen   (Bestiitigiingen  und  Modifikationen)    iiber  die 

Bedeutung  der  4  Reaktionen   (Pleocytose,  Phase  I.  Wassermann  Reaktion 

ira  Serum  und  im  Liquor  spinalis)   fiir  die  Diagnose  der  syphilidogenen 

Hirn-  und  Riickenmarkskrankheiten,  Dritte  Jahresvers.   d.  Ges.  deutscher 

Nervenarzte,  Ref.  x.  Ztschr.  f.  Xervenh.,  1910,  xxxviii,  291-307. 
Nonne  and  Apelt:     Tiber  fraktionierte  Eiweissausfalliuig  in  der  Spinalfliissig- 

keit,  Arch.  f.  Psychiat.,  1907,  xliii,  433. 
Pandy:     Uber  die  neue  Eiweissprobe  fiir  die  Zerebrospinalfliissigkeit,  Neurol. 

Zentralbl.,  1910,  xxix,  915. 
Redlich,   Potzl,   and   Hess:      Untersuchungcn    iiber   das   Vcrhalten   des   Liquor 

cerebrospinalis  bei  der  Epilepsie,  Ztsch.  f.  ges.  Neurol,  u.  Psychiat.,  1910, 

ii,   715. 
Ross  and  Jones:     On  the  Use  of  Certain  New  Chemical  Tests  in  the  Diagnosis 

of  General  Paralysis  and  Tal>es,  Brit.   Med.   Jour.,   1909,  i,   1111. 
Seelman:      Simple  Test   for   Estimating  Chlorides   in   the  Urine   Founded   on 

Volhard's  Method,  Jour.  Lab.  and  Clin.  Med.,  1916,  i,  444. 
Swift   and   Ellis:      Method   of   Cell   Counting   in   Cerebrospinal    Fluid,    Jour. 

Exper.  Med.,  1913,  xviii,  164. 
Szecsi:      Zur    Technik    der    Chem.    und   Zytolog.    Untersuchung    der    Lumbal- 

fiiissigkeit,  Monatschr.  f.  Psychiat.  u.  Neurol.,  1910,  xxvii,  152. 


CHAPTER  VII 
CEREBROSPINAL  FLUID  IN  VARIOUS  DISEASES 

Uremia 

In  uremia  the  fluid  is  often  increased  both  in  amount  and 
pressure,  especially  if  there  are  convulsions.  The  cells  may 
or  may  not  be  increased  in  number.  The  chlorides  are  of- 
ten increased  to  0.8  or  0.85  gm.  per  100  c.c.  of  fluid.  The 
urea  is  greatly  increased  in  amount.  According  to  Locke- 
mann  and  Fiith  the  lactic  acid  in  the  fluid  is  also  increased 
in  amount. 

Diabetes  Mellitus 

The  cerebrospinal  fluid  is  normal  in  appearance  and  pres- 
sure in  cases  of  diabetes  mellitus.  It  is  chemically  nega- 
tive in  all  respects  but  in  its  sugar  content,  which  is  greatly 
in  excess  of  normal.  Foster  found  the  sugar  in  the  fluid  of 
12  cases  of  diabetes  to  vary  between  0.5  per  cent  and  3  per 
cent.  My  highest  finding  was  0.38  per  cent.  In  one  case  I 
found  the  sugar  content  in  the  cerebrospinal  fluid  to  be 
even  higher  than  that  of  the  blood.  Acetone  and  diacetic 
acid  may  also  be  found  in  large  amounts  in  the  cerebro- 
spinal fluid  of  patients  suffering  with  diabetes  mellitus. 

Chorea 
Dupre  £md  Damns  found  a  distinct  lymphocytosis  in  the 
cerebrospinal  fluid  of  a  chorea  in  a  boy  of  eighteen.  Ba- 
bonneix  found  a  lymphocytosis  in  two  of  five  cases. 
Thomas  and  Tinel  found  a  distinct  lymphocytosis  in  a  girl 
.of  thirteen,  suffering  from  chorea.  They  found  a  similar 
condition  in  two  of  four  other  patients  examined  a  few 
months  later.  Gatow-Gatovski  found  a  hypertension  in 
one  case  of  chorea. 

183 


184  CEREBKOSPINAL  FLUID 

Kichardier,  Lemaire  and  Sourdel  found  a  lymphocytosis 
in  twelve  out  of  fourteen  eases  and  hypertension  in  ten. 
In  three  cases,  symptoms  were  somewhat  relieved  by  punc- 
ture. A  number  of  French  observers  found  a  positive  Was- 
sermann  in  chorea  and  because  of  this  finding,  argued  in 
favor  of  the  specific  nature  of  chorea.  Leopold  and  Bern- 
hard  found  the  cerebrospinal  fluid  in  chorea  to  be  normal 
in  the  chemical  and  cytologic  tests.  In  the  cases  of  chorea 
that  came  under  my  observation,  the  cerebrospinal  fluid 
was  normal  in  all  respects,  including  the  Wassermann. 
The  cerebrospinal  fluid  in  Huntington's  chorea  or  hered- 
itary chorea  is  normal  in  all  respects.  The  various  experi- 
ences cited  above  incline  me  to  the  belief  that  the  exami- 
nation of  spinal  fluid  is  of  no  special  value  in  the  diagnosis' 
of  chorea. 

Epilepsy 

During  an  epileptic  attack  the  cerebrospinal  fluid  is  in- 
creased both  in  amount  and  in  pressure.  During  the  in- 
tervals betw^een  attacks,  both  the  amount  and  pressure  of 
the  fluid  may  or  may  not  be  increased.  In  epilepsy  due  to 
cerebrospinal  lues,  the  cells  and  globulin  content  are  in- 
creased ;  in  idiopathic  epilepsy,  both  the  cells  and  the  glob- 
ulin content  are  normal.  The  same  is  true  of  the  Wasser- 
mann reaction. 

Mongoliaai  Idiocy 

In  Mongolian  idiocy  the  cerebrospinal  fluid  is  often  nega- 
tive physically,  chemically  and  bacteriologically.  Steven- 
son found  the  fluid  from  a  large  number  of  cases  to  give  a 
typical  luetic  gold  chloride  curve.  Some  of  the  cases  exam- 
ined by  me  gave  positive  Wassermann  and  Lange  tests; 
many  of  them,  however,  gave  negative  tests.  I,  therefore, 
do  not  subscribe  to  the  view  that  all  cases  of  Mongolian 
idioc.Y  have  a  luetic  origin.  There  are  some  that  are  luetic 
by  coincidence  only. 


CEKEBROSPINAL   FLUID    IN    VARIOUS   DISEASES  185 

Psychoses 

In  psychosis  the  fluid  is  not  uniform.  In  alcoholic  psy- 
chosis the  quantity  of  fluid  that  can  be  removed  in  one  sit- 
ting is  greatly  increased,  it  often  being  possible  to  remove 
as  much  as  30  to  40  c.c.  easily.  The  pressure  is  greatly  in- 
creased in  this  type  of  psychosis,  running,  as  a  rule,  from 
150  to  300  mm.  of  water  in  height.  The  fluid  is  clear  and 
colorless ;  the  protein  is  not  increased,  and  the  cells  are  usu- 
ally normal  both  in  number  and  type,  although  occasion- 
ally I  have  noticed  an  increase  in  the  cell  count  ranging 
from  26  to  30  cells  per  cubic  millimeter. 

A  number  of  authors  Avho  have  been  able  to  detect  the 
presence  of  alcohol  in  the  cerebrospinal  fluid  of  alcoholic 
psychosis,  suggest  that  the  test  for  alcohol  be  used  for 
diagnostic  purposes. 

Dementia  precox  gives  a  normal  fluid  as  a  rule.  Rarely 
is  the  pressure  increased.  Paranoia  also  shows  no  devi- 
ation from  the  normal.  The  fluid  in  general  paresis  is  not 
constant.  In  the  majority  of  cases  the  fluid  is  increased  in 
amount  and  pressure;  the  cell  count  is  high,  30  to  40  per 
cubic  millimeter;  both  the  globulin  and  the  Wassermann 
tests  are  positive.  In  a  small  percentage  of  cases,  all  the 
findings  are  negative  with  the  exception  of  increase  in 
amount  and  pressure  of  the  fluid. 

Lues 

The  findings  in  the  cerebrospinal  fluid  in  acquired  lues 
depend  on  whether  or  not  the  nervous  system  is  involved. 
If  there  is  no  involvement  the  fluid  is  negative,  including 
the  Wassermann  test.  If  there  is  involvement  there  is  an 
increase  in  the  amount  of  the  fluid,  in  the  content  of  the 
protein,  and  in  the  number  of  the  cells  in  the  fluid,  the 
cells  being  principally  lymphocytes.  The  Wassermann  is 
also  positive. 

Nonne  speaks  of  four  reactions  in  connection  with  syph- 
ilis of  the  nervous  system:  positive    Wassermann  reaction 


186 


CEREBROSPIXAL  FLUID 


of  the  blood,  increased  globulin,  lymphocytosis  and  posi- 
tive Wassermann  reaction  of  the  cerebrospinal  fluid. 
Nonne's  results  may  be  summarized  in  Table  XLI. 


Table  XLI 


WA.SSERIViAXN 
TEST    IX    BLOOD 

PHASE   I 
GLOBILIN 

LYMPHO- 
CYTOSIS 

WASSEKMANX     TEST     IN 
CEREBROSPIXAL  FLUID 

General 
paresis 

Tabes 
without 
paresis 
Cerebro- 
spinal 
lues 

10070 

Positive 

60-70% 
Positive 

80-90%c 
Positive 

95-100% 
Positive 

85-90%, 
Positive 

95%, 
90%, 
100% 

100%  positive  if  large 

quantities  of  fluid  are 

used. 

100%  positive  if  large 

quantities  of  fluid  are 

used. 

100%  positive  if  large 

quantities  of  fluid  are 

used. 

In  syphilis  of  the  nervous  system  the  gold  chloride  test 
gives  a  positive  reaction  in  the  syphilitic  zone,  the  reaction 
varying  with  the  type  of  the  disea.se.  In  cerebrospinal 
lues  the  discoloration  is  in  Tubes  1,  2,  3,  4,  5,  and  6;  (Fig. 
38)  in  tabes  the  discoloration  is  inconstant,  but  is  usually  in 
Tubes  2,  3,  4,  and  5  and  sometimes  in  6.  (Figs.  39  and  41.) 
In  paresis,  the  discoloration  is  usually  in  the  first  six  tubes 
and  sometimes  also  in  the  seventh  and  eighth,  (Figs.  40  and 
42.) 

Table  XLU 


GENERAL 

CEREBROSPIXAL 

PARALYSIS 

.SYPHILIS 

Num- 

Num- 

Num- 

ber of 

ber  of 

ber  of 

cases 

% 

ca.ses 

% 

cases 

% 

Marie  and  I^vaditi 

39 

73 

9 

66.6 

Marie,  Levaditi  and  Yamanouchi . . . 

30 

93 

Stertz 

45 

88.8 

5 

60 

8 

0 

Noguchi  and  Moore 

60 

73 

11 

54.5 

6 

50 

Wassermann  and  Plant 

41 

88 

Morgenroth  and  Stertz 

8 

100 

Plant 

54 

9 

90 
90 

9 

50 

4 
16 

0 

Nonne 

25 

Schutze 

12 

66.6 

Marinesco 

35 

94 

15 

53 

Smith  and  Candler 

64 

92.1 

Noguchi,  Rosanoff,  and  Wiseman. . . 

56 

87.5 

Total 

432 

90 

52 

56.2 

34 

19 

CEREBROSPINAL    FLUID    IN    VARIOUS   DISEASES 


187 


LANGE  COLLOIDAL  GOLO  TEST 

1 
1 

o 

g 

s 

s 

3 

J 

_i 

S 

1 

8 

5  Clear 
4  Pale  Blue 



3  Blue 

A 

<f- 

^^ 

2  Violet 

/^ 

J 

\ 

1  Red  Blue 

/ 

> 

ST 

ORed 

" 

Fig.    }>'&. — Case    of   cerebrospinal    lues.      Wassennann   +  +  + +. 


LANGE  COLLOIDAL  GOLD  TEST 

2 

o 

S 

g 

o 

.% 

-^ 

..i 

^  « 

8 

5  Clear 

4  Pale  Blue 

3  Blue 

)f 

2  Violet 

^A 

1  Red  Blue 

^ 

■Si^ 

H^ 

ORed 

I 

Vk- 

dj— 

.M. 

Fig.    39. — Case   of   tabes. 


LAIMGE  COLLOIDAL  GOLD  TEST 

2 

o 

S 

s 

§ 

J 

s 

(0 

J 

J 

8 

S  Clear 

^ 

" 

"k 

4  Pale  Blue 

\ 

3  Blue 

I 

2  Violet 

1 
1 

\ 

1  Red  Blue 

1 

i 

i 

^ 

s^ 

ORed 

M- 

Fig.    40. — Case    of   general    paresis.      Wassermmn   +  + +. 


188  CEREBROSPIXAL  FLUID 

The  incidence  of  positive  Wasserman  reaction  in  the 
cerebrospinal  fluid  of  lues  is  seen  from  Table  XLII  of 
Noguchi. 

Hydrocephalus 

As  was  pointed  out  in  the  chapter  on  normal  cerebro- 
spinal fluid,  the  older  writers  considered  the  cerebrospinal 
fluid  of  liydrocephalus  as  normal  fluid.  Recent  investiga- 
tions have  corroborated  the  truth  of  this  observation. 
With  the  exception  of  the  increase  in  the  amount  of  the 
cerebrospinal  fluid,  the  fluid  of  hydrocephalus  shows  no 
chemical,  physicochemical  or  bacteriologic  changes  of  any 
kind.  Only  infrequently  does  one  find  an  increase  in  the 
protein  content  of  hydrocephalic  fluid.  The  amount  of  fluid 
which  can  be  withdrawn  from  the  subarachnoid  space  de- 
pends on  the  form  of  the  hydrocephalus,  whether  it  is  in- 
ternal or  external.  If  the  foramina  of  Magendie  and 
Luschka  are  blocked,  very  little  fluid  may  be  obtained  by 
lumbar  puncture.  If  the  communication  is  open  a  great 
deal  of  fluid  may  be  obtained  by  lumbar  puncture.  The 
pressure  also  depends  on  the  amount  of  cerebrospinal  fluid 
in  the  subarachnoid  of  the  cord,  being  greatly  increased 
where  there  is  free  communication. 

Spina  Bifida 

The  fluid  is  usually  increased  in  amount  in  this  condi- 
tion, as  is  the  protein. 

Hemorrhage  of  the  Brain 

Cerebrospinal  fluid  removed  soon  after  the  hemorrhage 
occurs  is  bright  red  in  color  due  to  the  admixture  of  the 
blood;  and  contains  many  red  and  Avhite  blood  cells.  As 
time  progresses  the  cerebrospinal  fluid  becomes  more  yel- 
low in  color  and  the  red  cells  become  less  in  number.  The 
amount  of  fluid,  as  a  rule,  is  not  increased.  The  protein  is 
increased  due  to  the  addition  of  the  protein  from  the  blood. 
All  other  tests  are  negative. 


CEREBROSPINAL   FLUID   IN   VARIOUS   DISEASES  189 

Tumors  of  the  Brain 

In  tumors  of  the  brain,  the  amount  of  cerebrospinal  fluid 
may  or  may  not  be  increased.  The  protein  is  usually  not 
increased.  Occasionally  one  finds  an  increase  in  the  num- 
ber of  the  cells,  all  of  which  are  lymphocytes. 

Compression  of  the  Cord 

Compression  of  the  spinal  cord  gives  rise  to  a  number  of 
manifestations  of  the  cerebrospinal  fluid.  In  tumors  of 
the  Cauda  equina  and  conns  medullaris  the  Froin's  syn- 
drome usually  makes  its  appearance.  The  syndrome  shows 
the  following  characteristics:  (1)  xanthochromia  or  yel- 
lowish discoloration  of  the  cerebrospinal  fluid;  (2)  massive 
coagulation  of  the  fluid;  (3)  an  increased  number  of 
lymphocytes. 

In  tumors  situated  at  higher  levels  of  the  cord,  there  is 
an  excess  of  globulin  present,  but  no  increase  of  the  cells. 
There  may  or  may  not  be  a  yellowish  discoloration  of  the 
fluid.  In  extramedullary  compression  of  the  cord  there  is 
usually  a  yellow  discoloration  of  the  fluid  and  an  increase 
in  the  globulin,  but  no  increase  in  the  cells.  Discoloration 
of  the  fluid  alone,  does  not  indicate  compression  of  the  cord, 
as  this  condition  may  be  due  to  the  presence  of  an  old 
hemorrhage  of  the  brain,  or  even  to  a  puncture  of  the 
plexus  of  veins  surrounding  the  cord. 

Encephalitis 

It  is  difficult  to  establish  a  diagnosis  of  encephalitis  dur- 
ing life.  After  death  encephalitis  is  seen  as  a  feature  of 
poliomyelitis,  of  meningitis,  and  of  hydrocephalus.  The 
cerebrospinal  fluid  in  encephalitis,  therefore,  responds  to 
the  condition  it  accompanies.  In  poliomyelitis  the  fluid 
shows  the  changes  of  this  disease ;  in  meningitis  it  gives  the 
reactions  typical  of  the  organism  causing  the  infection.  In 
encephalitis  following  acute  infectious  diseases,  such  as 


100  CEREBROSPIJiTAL  FLUID 

pertussis  and  measles,  the  cerebrospinal  fluid  is  increased 
in  amount  and  in  pressure.  The  cells  are  either  normal  or 
slightly  increased  in  number.  The  globulins  are  not  in- 
creased, as  a  rule.  In  the  recent  epidemic  of  encephalitis 
lethargica  the  cerebrospinal  fluid  was  colorless  and  showed 
a  slight  increase  in  the  cell  count  and  in  the  globulin 
content. 

Meningism 

In  many  infectious  diseases,  notably,  pneumonia  and 
grippe  and  cases  of  otitis  media  and  also  in  some  cases  of 
intestinal  intoxication,  there  are  often  symptoms  of  cere- 
bral irritation,  simulating  a  meningitis,  although  no  bac- 
teria are  found  in  the  fluid  and  no  meningeal  exudate 
makes  its  appearance.  To  cases  of  this  character,  E.  Dupre 
has  given  the  name  of  meningism.  The  fluid  in  these  con- 
ditions is  generally  increased  in  amount,  sometimes 
even  to  the  same  extent  as  in  a  severe  case  of  meningitis. 
The  pressure  of  the  fluid  is  also  higher  than  normal.  The 
color,  however,  is  unchanged  and  the  number  of  cells  is  in- 
creased only  slightly  or  not  at  all.  The  globulin  as  well 
as  the  bacteriologic  tests  are  usually  negative.  Only  occa- 
sionally is  there  an  increase  in  the  globulin  and  in  the  cells. 
Caution,  however,  must  be  exercised  not  to  make  a  prema- 
ture diagnosis  of  meningism  in  all  instances  of  negative 
findings  of  the  fluid,  for  it  frequently  happens  that  cases  of 
tuberculous  meningitis  and  poliomyelitis  in  the  early  stages 
of  the  disease,  give  no  other  changes  in  the  cerebrospinal 
fluid  but  an  increase  in  the  amount  of  the  fluid. 

Tuberculous  Meningitis 

The  amount  of  fluid  in  tuberculous  meningitis  varies 
with  the  stage  of  the  disease,  being  greater  in  the  initial 
than  in  the  paralytic  stage.  The  pressure  at  the  onset 
of  the  disease  is  very  high,  ranging  between  300  and  700 
mm.  water  in  height.     The  pressure  remains  high  during 


CEREBROSPINAL   FLUID   IN   VARIOUS   DISEASES  191 

the  irritative  stage  l)ut  decreases  during  tlie  stage  of  coma. 
The  fluid  is  usually  clear  and  transparent  througliout  the 
disease,  althougli  occasionally  it  becomes  opalescent;  it 
shows  a  heavy  foam  on  shaking.  On  standing  from  one 
hour  to  an  entire  day  a  pellicle  forms,  tlie  pellicle  being 
generally  suspended  in  the  center  with  processes  project- 
ing from  its  sides.  There  is  an  increase  in  tlie  number 
of  cells  which  range  from  30  to  150  per  c.mm.,  most 
of  them  being  small  lymphocytes,  although  early  in  the 
disease  there  may  be  a  preponderance  of  polj^morphonu- 
clear  leucocytes.  The  protein  in  the  fluid  is  also  greatly 
increased  in  amount.  The  albumin  content  ranges '  be- 
tween 0.1  and  0.2  per  100  c.c.  in  adults.  Fibrin  and  fibrin- 
ogen are  present  in  small  amounts  as  is  indicated  by  the 
presence  of  the  pellicle  in  the  fluid.  Albuniose  and  pep- 
tone are  absent,  as  a  rule,  as  is  also  mucin. 

The  fluid  of  tuberculous  meningitis  also  shows  other 
variations  from  normal.  The  permanganate  index  is  above 
2  as  compared  with  the  index  in  nonmeningitic  fluid  which 
is  below  2.  The  chlorides  are  lessened  in  tuberculous  men- 
ingitis, usually  running  below  0.6  gm.  per  100  c.c.  and  some- 
times falling  as  low  as  0.5  gm.  per  100  c.c.  The  sugar  con- 
tent varies,  sometimes  equaling  the  amount  in  normal  fluid 
and  sometimes  falling  below  that  of  normal.  As  a  rule, 
however,  the  sugar  content  ranges  between  0.5  gm.  and  0.6 
gm.  per  100  c.c.  Phosphates,  according  to  Apelt  and 
Schumm,  are  present  in  amounts  varying  between  0.0034 
and  0.0049  per  cent. 

The  physicocheinical  constants  also  show  a  deviation 
from  normal.  The  average  density  is  given  as  1.002,  al- 
though in  my  cases,  I  found  it  to  vary  between  1.00626 
and  1.00693.  " 

The  viscosity  varies  between  1.0693  and  1.0694.  The 
conductivity  is  given  by  Fuchs  and  Rosenthal  as  ranging 
from  0.097  and  0.0225,  with  an  average  of  0.0127.  The 
freezing  i^oint  is  usually  lowered  running  between  0.45  and 
0.55. 


192 


CEREBROSPINAL  FLUID 


The  H-ion  concentration  averages  a  Ph  of  from  7.4  to 

7.6  immediately  after  the  removal  of  the  fluid  from  the  body, 
with  an  increase  in  the  alkalinity  npon  standing,  so  that 
one-half  hour  after  withdrawal  the  Ph  of  the  fluid  becomes 

7.7  or  7.8.     Twenty-four  hours  after  withdrawal   the  Ph 


LANGE  COLLOIDAL  GOLD  TEST 

o 

g 

o 

s 

s 

^^ 

e 
J' 

-^ 

..I 

8 

5Cleu 

4  Pale  Blue 

3  Blue 

j 

/*^ 

U 

^ 

2  Violet 

/ 

\ 

1  Red  Blue 

Jf- 

Iv 

r 

V 

J 

ORed 

r 

L 

■^ 

Fig.    43-A. — Case   of   tuberculous   meningitis. 


LANGE  COLLOIDAL  GOLD  TEST 

o 

o 

§ 

s 

1 

J 

-^ 

-'- 

J 

8 

5  Clear 

4  Pale  Blue 



3  Blue 

2  Violet 

w — 

-  ^ 

^t 

V 

V 

1  Red  Blue 

/ 

^ 

\ 

»t  '  «  V 

— w* 

ORed 

*"  i  ■» 

Fig.    43-B. — Case    of    tuberculous    meningitis. 

becomes  8.1,  8.2  or  even  higher.     The  alkali  reserve  runs 
parallel  with  the  H-ion  concentration. 

The  gold  chloride  reactions  give  a  discoloration  corre- 
sponding to  Tubes  5,  6,  and  7,  sometimes  to  Tubes  7,  8,  or  9. 
(Figs.  43  and  44.)  The  ninhydrin  test  shows  a  discolora- 
tion with  the  fluid  of  tuberculous  meningitis. 


CEREBKOSPINAL   FLUID   IN    VARIOUS   DISEASES  193 

The  cataplioresis  shows  most  of  the  protein  moving  to- 
ward the  anode.  Upon  evaporation  long  crystals  form  in 
the  fluid.  The  sulphosalicylic  mercuric  chloride  ratio  is 
marked,  the  precipitate  with  mercuric  chloride  being 
three  times  as  great  as  that  of  the  sulphosalicylic  on  stand- 
ing. 

Tubercle  bacilli  are  found  in  the  centrifuged  fluid  only 
after  a  careful  search.  They  are  often  found  more  easily 
in  the  pellicle.  Inoculation  of  the  cerebrospinal  fluid  of 
tuberculous  meningitis  in  guinea  pigs  produces  a  miliary 
tuberculosis  in  the  animal  in  course  of  one  to  six  weeks. 

From  a  diagnostic  standpoint  the  following  are  the  most 
important  changes  in  the  cerebrospinal  fluid  of  tubercu- 
lous meningitis:  Increase  in  amount  and  pressure,  increase 
in  the  number  of  cells  with  a  relative  lymphocytosis,  posi- 
tive Noguchi,  Ross-Jones,  and  Nonne  tests,  sulphosalicylic 
mercuric  chloride  ratio,  high  permanganate  index,  low 
chlorides,  Lange  curve,  and  above  all  the  presence  of  tu- 
bercle bacilli  in  the  fluid,  and  the  development  of  tubercles 
in  guinea  pigs  after  inoculation. 

The  following  case  w^ill  illustrate  the  cerebrospinal  fluid 
findings  in  a  case  of  tuberculous  meningitis: 

D.  H.,  eleven  and  one-half  years  of  age,  entered  the  hospital  complain- 
ing of  headache,  vomiting,  extreme  constipation,  anorexia,  and  weakness. 
The  onset  was  slow  with  vomiting  and  headache,  the  vomiting  being  pro- 
jectile in  type.  The  patient  became  listless  and  sleepy.  Examination 
showed  marked  symptoms  of  meningeal  irritation.  A  spinal  puncture  was 
performed.  The  fluid  obtained  was  clear  and  under  marked  pressure.  The 
cell  count  showed  320  cells  per  cubic  millimeter,  98  per  cent  of  which  were 
lymphocytes  and  2  per  cent  polymorphonuclear  leucocytes.  The  Noguchi 
and  Ross-Jones  globulin  tests  were  strongly  positive.  The  permanganate  index 
was  3.0.  The  mercuric  chloride  sediment  was  four  times  the  size  of  the  sulpho- 
salicylic sediment.  The  direct  smear  showed  no  organisms.  The  blood  showed 
80  per  cent  hemoglobin,  5400  leucocj-tes  per  cubic  millimeter,  of  which,  5S 
percent  were  neutrophiles,  20  per  cent  small  mononuclear  and  12  per  cent  large 
mononuclear.  The  Widal  reaction  was  negative,  so  were  the  blood  cultures. 
The  child  became  progressively  worse  and  another  spinal  puncture  was  done 
the  next  day  with  practically  the  same  findings  as  the  first  specimen  with 
the  additional  finding  of  a  pellicle  when  the  fluid  was  allowed  to  stand. 
A    third    puncture    showed     all     globulin     tests    to    be    positive,     the     gold 


194  CEREBROSPINAL  FLUID 

chloride  reaction  was  also  characteristic  of  tuberculous  meningitis.  The 
patient  died  after  staying  twelve  days  in  the  hospital.  The  postmortem 
showed  a  grayish  white,  purulent  exudate  at  the  base  of  the  brain,  meas- 
uring 0.5  cm.  in  thickness,  the  exudate  covering  the  region  of  the  hypo- 
physis and  the  right  optic  nerve.  A  part  of  it  also  extended  to  the  right 
of  the  longitudinal  fissure  in  the  region  of  the  parietal  lobe.  The  exudate 
showed  the  presence  of  tubercle  bacilli.  Caseated  glands  Avere  found,  in  the 
hilus  of  the  lung. 

Meningococcus  Meningitis 

In  meningococcus  meningitis,  the  amount  of  the  cerebro- 
spinal fluid  is  increased,  and  as  a  rule,  20  to  40  c.c.  can 
easily  be  removed  by  one  lumbar  puncture.  This  increase 
in  the  amount  of  the  fluid  is  a  constant  feature  of  meningo- 
coccus meningitis  throughout  the  disease.  Only  very  sel- 
dom does  it  happen  that  the  amount  of  the  fluid  is  not  in- 
creased. Cases  of  this  kind  usually  have  an  occlusion  of 
the  subarachnoid  space  somewhere  along  the  tract  of  the 
cerebrospinal  stem. 

The  pressure  of  the  fluid  in  meningococcus  meningitis  is 
also  increased  ranging  between  300  to  700  mm.  water  high. 
In  two  of  my  cases  the  pressure  was  as  high  as  800  mm.  of 
water. 

The  color  of  the  fluid  of  meningococcus  meningitis  varies 
from  a  slight  opalescence  at  the  onset  of  the  disease  to  a 
yellowish  green  later  in  its  course.  The  yellowish  green 
color  is  the  product  of  the  meningococcus.  On  standing  it 
sometimes  becomes  a  pronounced  green.  The  fluid  contin- 
ues turbid  throughout  the  course  of  the  disease.  It  rarely 
happens  that  the  fluid  in  the  early  stages  of  epidemic  men- 
ingitis is  clear  and  colorless.  On  standing  one-half  hour  or 
longer  the  fluid  forms  a  sediment  that  changes  in  character 
with  the  development  of  the  disease. 

(a)  In  the  early  stages  of  the  disease,  the  pellicle  is  made 
up  of  a  yellowish-white  network,  the  reticuli  being  close 
together  and  forming  an  opaque  layer.  The  upper  portion 
of  the  network  is  balloon-  or  dome-shaped  and  the  base  or 
lower  portion  is  flattened  in  appearance.     The  whole  net- 


CEREBROSPINAL   FLUID    IN    VARIOUS    DISEASES 


195 


work  resembles  a  small  bursa.  It  usually  does  not  reach 
the  upper  level  of  the  fluid  and  generally  it  is  seen  inclin- 
ing toward  one  side  of  the  tube. 

(b)  In  the  more  advanced  stages  of  meningitis,  the  sedi- 
ment formation  is  firmer.  It  generally  spreads  out  along 
one  side  of  the  tube  in  the  form  of  a  heavy  film. 

(c)  In  still  more  advanced  cases,  a  sediment  of  yellow 
granules  may  be  seen  attached  to  one  side  of  the  tube. 
These  granules  are  an  indication  that  the  disease  has  pro- 
gressed to  an  advanced  stage. 

(d)  In  the  very  grave  cases  the  sediment  is  thick  and 
falls  by  gravity  to  the  bottom. 


LANGE  COLLOIDAL  GOLD  TEST 

e 

g 

S 

S 

3 

J 

J 

I 

I 

s 

5  Clear 

4  Pale  Blue 

1 

A. 

3  Blue 

f 

f  ^ 

vr 

2  Violet 

X 

1  Red  Blue 

i    V     . 

_  w.i 

r 

-ir'l 

ORea 

i 

Fig.   46. — Case   of   meningococcus    meningitis. 

When  the  meningitic  process  recedes,  the  pellicle  or  sedi- 
ment takes  on  a  character  the  reverse  of  the  one  that  ap- 
peared at  its  formation.  The  chemical  changes  are  marked. 
The  organic  index  determined  by  the  permanganate  is 
high,  ranging  between  5  and  7.  The  protein  content  is 
greatly  increased  ranging  between  1  and  7  per  cent.  The 
Noguchi,  Koss-Jones,  Nonne  and  Pandy  globulin  tests  are 
strongly  positive.  A  3  per  cent  sulphosalicylic  acid  solu- 
tion gives  a  heavy  sediment  on  standing,  measuring  from 
10  to  20  mm.  in  height,  while  a  1  per  cent  mercuric  chloride 
solution  gives  a  sediment  much  lower  than  the  sulpho- 


196  CEREBROSPIJfAL  FLUID 

salicylic  acid.  The  sugar  is  usually  absent  or  greatly  di- 
minished during  the  active  stage  of  the  disease.  Lactic 
acid  is  present  in  the  fluid  in  large  quantities.  The 
chlorides  are  usually  the  same  as  normal,  although  they 
may  be  present  in  quantities  less  than  normal. 

Among  the  physicochemical  changes  that  take  place  in 
meningococcic  meningitis  the  following  are  important: 
Cataphoresis  shows  that  the  protein  migrates  to  the  cath- 
ode pole.  The  H-ion  concentration  is  increased  and  it  con- 
tinues high  for  a  long  time  after  the  removal  of  the  fluid 


•^  ^  '•% . 


* 


\ 


Fig.    47. — Photomicrograph    showing    direct    smear    from    cerebrospinal    fluid    of    case    of 
meningococcus  meningitis. 

from  the  body.  The  alkali  reserve  does  not  run  parallel 
with  the  H-ion  concentration.  The  viscosity  is  1.0434  to 
1.0735.  The  gold  chloride  test  shows  the  greatest  discolor- 
ation in  Tubes  7,  8,  and  9  (Figs.  45  and  46). 

The  cytologic  changes  are  distinct.  The  leucocytes  are 
increased  in  number,  varying  from  50  to  several  thousands 
per  cubic  millimeter.  The  greatest  percentage  of  the  cells 
(90  to  98  per  cent)  is  made  up  of  polymorphonuclear  leuco- 
cytes, although  the  lymphocytes  are  also  present  in  greater 
number  than  in  normal  fluid. 

The  bacteriologic  findings  are  fairly  constant.    A  gram- 


CEREBROSPINAL   FLUID    IN    VARIOUS   DISEASES  197 

negative  biscuit- shaped  organism  is  usually  found  in  the 
direct  smear  within  the  leucocytes,  some  being  found  also 
outside  of  the  leucocytes  (Fig  47).  The  number  of  or- 
ganisms found  in  the  smear  of  epidemic  meningitis  is  not 
nearly  so  great  as  that  found  in  the  smears  from  pneumo- 


Fig.  48. — Twenty-four-hour  culture  of  meningococci  grown  on  ascitic  dextrose  agar. 
The  culture  which  has  been  originally  obtained  from  a  case  of  meningococcus  menin- 
gitis has  been  transplanted  several  times  on  artificial  media,  hence  the  heavy  growth  in 
twenty-four  hours. 

COCCUS  fluid.  It  sometimes  happens  that  early  in  the  disease 
the  organisms  in  the  direct  smear  are  very  scanty  in  num- 
ber, but  after  the  first  or  second  dose  of  antimeningococcic 
serum,  there  is  a  shower  of  organisms  in  the  fluid. 


198  CEREBROSPINAL  FLUID 

On  ascitic  dextrose  agar,  the  meningococci  usually  grow 
in  pure  culture  (Figs.  48  and  49)  although  it  is  not  al- 
ways easy  to  grow  them.  The  meningococci  can  be  differ- 
entiated from  the  pneumococci  by  the  gram  stain,  the  me- 
ningococci being  gram-negative  and  the  pneumococci  gram- 
positive.  It  is  also  possible  to  differentiate  the  two  by  the 
agglutination  test.  On  the  other  hand,  it  is  very  difficult  to 
differentiate  the  meningococci  from  other  gram-negative 
cocci  such  as  gonococeus,  micrococcus  catarrhalis,  and  dip- 
lococcus  mucosus.    However,  since  these  organisms  rarely 


-      •         ••' 


« 


Fig.  49. — Photomicrograph  of  pure  meningococcus  culture.     Twenty-four-hour  growth. 

ever  produce  meningitis  it  is  seldom  necessary  to  take  them 
into  consideration. 

Occasionally  it  happens  that  a  case  of  meningitis  shows 
meningococci  in  the  cerebrospinal  fluid  both  in  the  direct 
smear  and  in  the  culture,  but  several  days  later  exami- 
nation of  the  fluid  shows  both  meningococci  and  pneumo- 
cocci or  pneumococci  alone.  Such  cases  have  been  re- 
ported by  Netter  and  Salonier,  by  Mathers  and  by  Fitzger- 
ald. Two  such  cases  of  mixed  infection  also  came  under 
my  observation. 


CEREBROSPINAL   FLUID   IN   VARIOUS   DISEASES  199 

One  must,  however,  be  careful  in  his  staining  technic 
to  avoid  reaching  erroneous  conchisions.  Above  all, 
even  when  the  existence  of  a  mixed  infection  of  me- 
ningococcus and  pneumococcus  has  been  established  one 
must  not  neglect  giving  the  patient  antimeningococcus  se- 
rum, as  this  is  the  only  hope  left  for  him. 

After  several  doses  of  antimeningococcus  serum  have 
been  administered  to  the  patient  and  the  case  shows  im- 
provement, the  cerebrospinal  fluid  gradually  changes  in  all 
respects.  The  fluid  becomes  less  and  less  turbid  by  de- 
grees, the  color  remains  yellow  because  of  the  color  of  the 
serum,  but  it  loses  its  greenish  tint.  The  amount  with- 
drawn at  each  sitting  is  smaller  than  at  the  height  of  the 
disease;  the  pressure  becomes  lower,  the  protein  content 
becomes  less,  and  the  physicochemical  changes  grow  less 
and  less  distinct.  The  cells  decrease  in  number  and  the  type 
of  cell  changes  from  polymorphonuclear  to  lymphocyte. 
The  bacteria  also  gradually  disappear  after  several  doses 
of  serum. 

The  following  reports  give  the  average  findings  in  the 
cerebrospinal  flu,id  of  meningococcus  meningitis : 

I.  M.  G.,  Fluid  cloudy,  cell  count  51,  differential  count  90  per  cent  poly- 
morphonuclear leucocytes.  Noguehi,  Ross-Jones,  and  Nonne,  positive.  Sulpho- 
salicylie  gives  heavy  precipitate,  mercuric  chloride  produces  only  turbidity. 
Sugar  0.01  per  cent.    No  bacteria  found  in  direct  smear. 

Twenty-four  hours  later :  Gram-negative  organism  on  ascitic  dextrose 
agar  agglutinating  in  1:200  dilution.  Sulphosalicylic  sediment  measures  20 
mm.,  mercuric  chloride  5  mm.,  albumin  by  modified  Esbach  0.1  per  cent. 

Fluid  examined  after  administration  of  30  c.c.  of  antimeningococcus  serum, 
— very  cloudy.  Cell  count  218;  Noguehi,  Ross-Jones,  and  Nonne  positive.  Sul- 
phosalicylic gives  heavy  precipitate,  mercuric  chloride  only  turbidity.  Sugar 
absent.     Gram-negative  cocci  in  smear. 

Twenty-four  hours  later:  Gram-negative  organisms  in  culture,  agglutinat- 
ing in  1:200  dilution,  sulphosalicylic  sediment  24  mm.,  mercuric  chloride  6 
mm.,  albumin  0.15  per  cent. 

Fluid  withdrawn  after  administration  of  120  c.c.  of  antimeningococcus 
serum.  Appearance  yellow.  Cell  count  14.  Differential  count  50  per  cent 
Ijolj'morphonuclears.  Glolmlin  tests  slightly  positive.  Sugar  0.07  per  cent. 
No  organisms  in  direct  smear  or  in  culture. 


200  CEREBROSPINAL  FLUID 

II.  E.  C.  Fluid  turbid.  Cell  count  14,000;  differential  count  95  per 
cent  polymorphonuclear;  occasional  endothelial  cell.  Noguchi,  Ross- Jones, 
and  Nonne  positive.  Sulphosalicylie  very  heavy  precipitate;  mercuric  chloride 
turbid.  Sugar  absent.  Chlorides  0.6  per  cent.  Permanganate  index  4.0. 
Gram-negative  intracellular  diplococci. 

Twenty-four  hours  later:  No  growth  on  ascitic  dextrose  agar.  Albumin 
0.15  per  cent.    Sulphosalicylie  sediment  18  mm. ;  mercuric  chloride  6  mm. 

Forty-eight-hour  report:  Gram-negative  diplococci  agglutinating  anti- 
meningitic  serum  in  1:250  dilution. 

Pneumococcus  Meningitis 

In  pneumococcus  meningitis  the  cerebrospinal  fluid  is 
greatly  increased  in  amount,  ranging  between  20  and  50 
c.c.  of  fluid  in  one  puncture.  The  color  of  the  fluid 
varies  according  to  the  stage  of  the  disease,  but  as  a  rule, 
it  is  pearly  gray,  in  contrast  to  the  greenish  yellow  of  the 
fluid  of  meningococcus  meningitis.  On  standing,  a  heavy 
sediment  forms  which  is  usually  fibrinous  in  character,  the 
amount  of  fibrin  being  greater  in  the  pneumococcic  than 
in  the  meningococcic  form. 

In  pneumococcus  meningitis,  the  amount  of  protein  is 
greatly  increased  ranging  between  0.1  and  0.7  per  cent. 
Thus  all  globulin  tests  are  strongly  positive.  The  amount 
of  sugar  is  less  than  normal  and  very  often  is  absent  alto- 
gether. Chlorides  are  generally  present  in  the  same  amount 
as  in  normal  fluid,  ranging  between  0.6  and  0.74  grams  per 
100  c.c.  of  cerebrospinal  fluid. 

The  physicochemical  changes  are  usually  the  same  as 
in  the  meningococcus  type.  The  cells  in  the  fluid  are  nu- 
merous, numbering  as  high  as  1000  or  more  per  c.mm. 
The  greatest  percentage  of  the  cells  are  polymorphonu- 
clear leucocytes.  The  pneumococci  Avhich  are  usually 
found  with  ease  in  the  direct  smear  are  present  in  great 
numbers.  At  times  there  are  many  gram-positive  bacteria 
in  the  smear  and  very  few  cells.    (Fig.  50.) 

The  bacteria  often  are  arranged  in  chains  of  four  or  six, 
thus  making  it  difficult  to  differentiate  pneumococcus  from 


CEREBROSPINAL   FLUID    IN    VARIOUS   DISEASES 


201 


.  *  •  •  j».  *  -  . 

J -""'.* ' ':^V  "V-k^** 'r-»V  •  - 


Fig.    50. — Photomicrograph  of  smear  from   cciL-liruspiiial  fluid  of  piieumococcus  meningitis. 


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Fig.    .SI. — Photomicrograph    showiiii,'    'linit    snuar    from    cerebrosi)inal    fluid    of    case    of 
mixed    streptococcus    aiul    i>neimiococcus    meningitis. 

streptococcus.  However,  tlie  fluid  of  piieumococcus  men- 
ingitis contains  a  more  fibrinous  pellicle  than  does  that  of 
streptococcus.  The  capsule  stain  is  also  of  assistance  in 
differentiating  between  tlie  two  bacteria.    The  final  diag- 


20^  CEREBKOSPIKAL    FLUID 

nosis,  however,  must  rest  on  tlie  character  of  tlie  culture 
aud  on  the  agglutinative  properties  of  the  organism.  At 
times,  however,  there  is  a  mixed  pneumococcus  and  strep- 
tococcus infection  of  the  meninges  (Fig.  51). 

E.  B.,  three  and  one-half  months  old,  brought  to  hospital  with  a  history 
of  fever  and  rigidity  of  neck  of  one  week's  duration.  Physical  examination 
showed,  in  addition  to  rigidity  of  neck,  a  positive  Kernig  sign,  positive  Brud- 
zinsky  and  twitchings  of  the  right  side  of  the  body.  The  cerebrospinal  fluid 
removed  by  lumbar  puncture,  was  increased  in  pressure  and  very  turbid.  The 
cells  numbered  1400  per  cubic  millimeter,  of  which  52  per  cent  were  poly- 
morphonuclear leucocytes,  and  48  per  cent  were  lymphocytes.  Noguchi, 
Eoss- Jones,  and  Nonne  globulin  tests  were  positive.  Sulphosalicylic  gave  a 
heavy  turbidity  and  mercuric  chloride  only  a  very  sliglit  turbidity.  The 
chlorides  were  0.66  per  cent.  Quantitative  protein  by  modified  Esbach  0.1 
per  cent.  The  gold  chloride  test  gave  a  discoloration  in  the  seventh,  eighth, 
and  ninth  tubes.  The  direct  smear  showed  gram-positive,  lanceolated  organ- 
isms, arranged  in  pairs,  which,  however,  did  not  agglutinate  with  either  Type 
I,  Type  II,  or  Type  II  antipneumococcus  serum. 

The  patient  became  progressively  worse.  Another  lumbar  puncture  was 
made  twelve  hours  later,  Imt  only  2  c.c.  of  very  thick  cerebrospinal  fluid  was 
obtained.  A  ventricular  puncture  was  thereupon  made  aud  25  c.c.  of  cere- 
brospinal fluid  was  obtained.  The  fluid  was  turbid  but  not  as  turbid  as  that 
obtained  by  lumbar  puncture.  The  cells  numbered  150  per  cubic  millimeter, 
the  globulin  tests  were  all  positive,  the  chlorides  read  0.74  per  cent  and  the 
direct  smear  showed  the  same  organism  as  in  the  first  fluid. 

Twenty  c.c.  of  polyvalent  antipneumococcus  serum  was  injected  into  the 
ventricle  by  gravity  method.  The  patient,  however,  grew  constantly  worse 
and  died  eighteen  hours  after  the  injection  of  the  serum. 

Streptococcus  Meningitis 

In  my  experience,  hemolytic  streptococci  were  found 
to  be  the  most  frequent  type  of  streptococcus  producing 
meningitis,  although  many  cases  of  nonhemolytic  strepto- 
coccus meningitis  also  came  to  my  attention. 

The  cerebrospinal  fluid  of  all  forms  of  streptococcus  men- 
ingitis is  very  turbid.  It  is  increased  in  amount  and  in 
pressure.  The  protein  content  is  also  increased  and  all 
globulin  tests  are  positive.  The  cells  are  also  increased 
and  90  to  95  per  cent  of  them  are  polymorphonuclear  leuco- 
cytes. The  streptococci  are  found  in  the  direct  smear  (Fig. 
51)  and  in  culture.    To  differentiate  between  the  types  of 


CEREBROSPINAL    FLUID    IN    VARIOUS    DISEASES  203 

streptococcus,  the  fluid  should  be  put  on  blood  agar.    The 
hemolytic  streptococci  will  produce  hemolysis. 

Influenza  Meningitis 

This  not  infrequent  form  of  meningitis  gives  an  in- 
creased amount  of  fluid  which  varies  in  color  from  a  slight 
opalescence  to  a  distinct  yellow.  The  cells  in  this  condi- 
tion are  increased  in  number  and  range  from  100  to  400 
per  c.mm.  As  a  general  rule,  the  cells  are  almost  entirely 
polymorphonuclears,  although  occasionally  one  may  find 
as  high  as  40  to  50  per  cent  of  the  cells  to  be  lymphocytes. 
Gram-negative  bacilli  are  found  extracellularly  in  the  di- 
rect smear  in  large  numbers.  (Figs.  52  and  53.)  However, 
a  special  medium  containing  hemoglobin  is  required  to 
groAV  the  influenza  bacilli. 

Colon  Meningitis 

Colon  meningitis,  typhoid  meningitis  and  gonococcus 
meningitis  have  been  reported  in  the  literature.  These 
conditions  are  very  rare,  however.  Their  findings  are  the 
same  as  those  manifested  in  other  forms  of  suppurative 
meningitis.  The  diagnosis  in  these  conditions  can  be  made 
upon  recovering  the  bacteria  from  the  cerebrospinal  fluid 
and  culture.  It  can  also  be  made  on  the  characteristic  ag- 
glutination tests. 

Syphilitic  Meningitis 

Chronic  syphilitic  involvement  of  the  meninges  is  rather 
frequent,  but  as  a  rule  remains  unrecognized,  giving  few 
symptoms  or  signs.  Acute  syphilitic  meningitis  is  less 
frequent,  but  it  does  occur  occasionally  and  one  must  al- 
ways keep  it  in  mind  in  cases  where  a  meningitis  exists 
and  where  the  exciting  organisms  can  not  be  recovered  from 
the  cerebrospinal  fluid  culture  and  where  the  clinical  symp- 
toms do  not  justify  a  diagnosis  of  either  tuberculous  men- 
ingitis or  poliomyelitis. 

The  cerebrospinal  fluid  in  acute  syi:)hilitic  meningitis  is 


204 


CEREBROSPIXAL    FLUID 


clear  or  slightly  opalescent.    It  is  moderately  increased  in 
amount,  generally  from  15  to  25  c.c.  of  cerebrospinal  fluid  at 


Fig.   52. — Photomicrograph   showing   direct    smear   from   cerebrospinal   fluid   of   case   of   in- 
fluenza   meningitis. 


%, 


Fig.    53. — Photomicrograph   of  pure   culture   of   influenza  bacilli. 

one  sitting.    The  fluid  is  moderately  increased  in  pressure. 
Tlie  globulin  tests  are  positive.     The  cells  are  greatly  in- 


CEREBROSPINAL    FLUID    IN    VARIOUS   DISEASES 


205 


creased  in  number,  running  between  100  to  600  cells  per 
cubic  millimeter,  GO  to  80  per  cent  of  the  cells  are  lympho- 
cytes. The  smears  and  cultures  are  negative  to  bacteria, 
but  on  careful  search  with  the  India-ink  method  one  may 
find  the  presence  of  Spirochete  pallida.  The  Wassermann 
is  positive.  The  Lange  gives  a  reaction  in  the  syphilitic 
zone. 

Cerebrospinal  Fluid  in  Poliomyelitis 

The  fluid  is  increased  in  amount  ranging  between  20  to 
50  c.c.  at  one  sitting. 

The  pressure  is  increased,  ranging  between  300  to  700 
mm.  of  water  in  height. 


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The  permanganate  index  is  slightly  above  the  normal 
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amount,  generally  giving  positive  globulin  tests,  although 
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The  gold  chloride  test  in  the  preparalytic  stage,  shows 
either  no  change  at  all,  or  a  change  in  the  luetic  zone  only. 
(Fig.  54.)  After  the  subsidence  of  the  acute  symptoms,  from 
the  second  to  the  twelfth  day,  the  reaction  may  be  most 
prominent  in  the  meningitic  zone.    The  cells  in  this  condi- 


206 


CEREBROSPIXAL    FLUID 


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CEREBROSPINAL   FLUID   IN   VARIOUS   DISEASES  207 

tion  are  increased  in  number,  90  per  cent  of  them  being  of 
tlie  small,  mononuclear  type.  The  increase  manifests  itself 
in  the  preparalytic  stage  and  lasts  fourteen  to  sixteen  days 
after  the  onset  of  paralysis.  The  cells  are  greatest  in  num- 
ber during  the  first  week  after  the  onset  of  paralysis.  The 
largest  percentage  of  cells  (60  to  90  per  cent)  is  of  the 
small  lymphocyte  type,  except  in  the  very  early  stage  of 
the  disease  when  the  predominating  cell  may  be  the  poly- 
morphonuclear. 

The  bacteriology  of  poliomyelitis  is  still  an  open  ques- 
tion. Flexner  and  Lewis  found  a  filtrable  virus.  Mathers, 
Nuzuin  and  Rosenow  report  the  finding  of  a  micrococcus 
in  the  brain  and  cord.  Nuzum  reports  the  presence  of  the 
coccus  in  the  cerebrospinal  fluid.  The  organism,  accord- 
ing to  these  authors,  is  grow^n  best  on  a  1  per  cent  glucose 
broth  medium,  incubated  under  aerobic  conditions.  Other 
workers  dispute  the  specificity  of  this  microorganism  in 
poliomyelitis.  At  the  present  state  of  our  knowledge  no 
positive  diagnosis  can  be  made  of  poliomyelitis  by  the 
fluid  findings  alone.  The  history  of  the  case  and  its  prog- 
ress must  always  be  taken  into  consideration  as  well. 

Bibliography 

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Ayer  and  Viets:  Spinal  Fluid  Findings  Characteristic  of  Cord  Compression, 
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Elsberg  and  Rochfort:  Xanthochromia  an<l  Other  Changes  in  the  Cerebro- 
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heiten,  Virchows  Arch.  Beiheft  1908,  p.  194. 
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Quincke :      tJber   Meningitis   serosa,   Samml.   klin.   Vortr.   v.*  Volkmann,   1893, 

p.  655. 
Redlich,  Potzl,  and  Hess:     Untersuehungen  iiber  das  Verhalten  des  Liquor  cere- 
brospinalis bei  der  Epilepsie,  Ztschr.  f.  d.  ges.  Neurol,  u.  Psychiat.,  1910, 

ii,  715;   ibid.,  1910,  iii,  492. 
Rist,  E.:     Xeue  Methoden,  etc.,  Centralbl.  f.  Bakteriol.  u.  Paras.,  1901,  xxx. 
Romheld :     Zur  Klinik  postdiptherischer  Lahmungen ;   Liquorbefund  bei  post- 

diptherischer  Pseudotabes,  Vortrag.  Ref.,  Neurol.  Centralbl..   1908,   1007. 
Rosenow,    Towne   and   Wheeler:      Etiology   of   Epidemic   Poliomyelitis,   Jour. 

Am.  Med.  Assn.,  1917,  Ixvii,  1202. 
Schottmiiller :      Meningitis  Cerebrospinalis   Epidemica    (Weichselbaum),   Miin- 

chen  med.  Wchnschr.,  1905,  lii,  617,  1683,  1729. 
Schottmiiller:      Zur    Bedeutung    einiger    Anaerobier    in    der    Pathologie,    Mit- 

teilungen  aus  d.  Grezgebeiten  d.  Med.  u.  Chir.,  xxx. 
Schottmiiller   and   Schumm :      Nachweisj  '-on  Alkohol  in  der  Spinalfliissigkeit 

von     Saufern,     Neurol.     Centralbl.,     1912,     xxxi,     1020,     Miiiiclicn     Med. 

Wchnschr.,  1910. 
Schultze:       Zur    Diagnostik    der    akuten    Meningitis,    Yerhandl.    d.    Cong.    f. 

inn.  Med.,  1S67,  p.  393. 
Staubli :      Meningismus   t^^1hosus   u.    Meningotyphus,   Deutsch.   Arch,   f .   klin. 

Med..  1904-1905,  Ixxxii.  90. 
WoUstein :     Influenza  Meningitis  and  its  Experimental  Production,  Am.  Jour. 

Dis.  Child.,  1911,  i,  42. 


CHAPTER  VIII 

INTRASPINAL  TREATMENT 

Whenever  there  is  a  specific  remedy  for  a  disease  of  the 
central  nervous  system,  it  is  of  the  utmost  importance 
tliat  the  remedy  be  brought  into  direct  contact  with  the 
central  nervous  system  as  early  as  possible.  Even  when 
no  specific  exists,  it  may  be  advisable  to  introduce  some 
form  of  medication  into  the  cerebrospinal  fluid.  The  in- 
jection is  made  either  intraspinally,  or  intraventricularly. 


Intraspinal   Treatment  of  Meningococcus  Meningitis 

The  reports  of  Flexner  and  his  associates,  and  the  ex- 
perience of  most  physicians,  have  established  the  fact  tliat 
the  best  and  most  successful  way  of  treating  meningococcus 
meningitis  is  by  means  of  antimoningococcus  serum.  The 
mortality  of  cases  of  meningitis  that  received  serum  has 
been  reduced  to  one-half,  in  some  epidemics  to  one-third  of 
the  mortality  of  cases  that  received  no  serum,  as  is  shown 
by  Table  XLIV  from  Sophian. 

Table  XLIV 

Effect  op  Antimeningococcus   Serum   on   Mortality   fuom    Epidemic 

Meningitis 


CASES  TREATED  WITH  SERUM 

Number 


Percentage 
Mortality 


CASES     TREATED 
WITHOUT    SERUM 

Percentage 
Mortality 


Flexner 

1,400 

31.4 

70-80 

Steiner 

2,280 

37.0 

77 

Netter 

100 

28.0 

49 

Dopter 

402 

16.44 

52.14 

Levy 

165 

18.18 

65 

Sophian 

161 

15.5 

209 


210  CEREBROSPINAL    l-LUID 

Tlie  antimeningococcus  serum  now  in  use  is  prej^ared  by 
repeated  injections  of  dissolved  meningococci  (culture 
autolysate  meningococci  extract)  into  a  horse  followed  by 
injections  of  live  meningococcus  cultures.  The  cultures 
used  are  of  various  strains  of  meningococci,  so  that  the 
serum  is  polyvalent. 

The  serum  is  tested  before  it  is  put  up  in  packages,  by 
one  of  several  methods :  the  complement-fixation  method, 
the  agglutination  test,  the  opsonin  content  and  the  animal 
protection  test.  In  England  the  agglutination  test  is  used 
very  extensively.  In  France  the  complement-fixation 
method  is  the  one  most  generally  employed.  In  America 
all  four  methods  are  used  by  various  manufacturers. 
McCoy,  Wayson  and  Corbitt  of  the  United  States  Public 
Health  Service,  accept  any  serum  which  passes  satisfac- 
torily, either  by  an  agglutination  or  complement-fixation 
test  as  a  suitable  serum  for  therapeutic  purposes. 

The  antimeningococcus  serum  is  usually  preserved  witli 
0.2  per  cent  to  0.3  per  cent  of  tricresol.  The  use  of  this  pre- 
servative has  given  rise  to  a  number  of  objections.  Kramer 
ascribes  some  of  the  deaths  that  had  occurred  after  the  in- 
jection of  antimeningococcus  serum  to  the  use^of  tricresol 
Avhich  he  claims  has  a  very  depressing  effect  on  the  medul- 
lary center.  It  has  been  found,  however,  that  of  the  dif- 
ferent preservatives  used,  tricresol  exerts  the  most  marked 
bactericidal  effect  on  the  ])acteria,  and  is  a  much  less  irritat- 
ing preservative  than  chloroform.  It  is  therefore  used  ex- 
clusively in  this  country  as  a  preservative  of  antimeningo- 
coccus serum. 

Whenever  a  case  presents  itself  that  shows  signs  and 
symptoms  of  meningitis,  and  gram-negative  cocci  in  the 
smear,  no  time  should  be  lost  in  injecting  the  patient 
with  antimeningococcus  serum.  AVe  may  even  go  a  step 
further  and  say  that  Avhenever  a  turbid  cerebrospinal  fluid 
is  obtained  antimeningococcus  serum  should  be  injected 
immediately  on  the  probability  that  the  case  is  one  of  epi- 


INTRASPINAL   TREATMENT  211 

demic  meningitis.  Of  late  tlie  intravenous  injection  has 
been  advocated,  but  even  when  intravenous  injection  of 
serum  is  employed  the  serum  should  be  injected  into  the 
cerebrospinal  canal  also  if  there  are  indications  of  the  pres- 
ence of  meningitis. 

The  following  is  the  technic  of  intraspinal  injection  of 
serum : 

A  lumbar  puncture  is  done  with  the  patient  lying  on  his 
side.  (The  entire  procedure  is  described  in  detail  in  Chap- 
ter III.)  If  the  fluid  removed  is  turbid,  15  to  30  c.c.  of 
cerebrospinal  fluid  is  withdrawn,  the  amount  depending 
upon  the  pressure  of  the  cerebrospinal  fluid  and  the  quan- 
tity of  serum  to  be  administered.  One  or  two  vials  of  anti- 
meningococcus  serum  which  have  been  kept  in  the  refrigera- 
tor are  warmed  in  w^arm  water  to  98  or  99°  F.  The  vial  con- 
taining the  serum  is  attached  to  a  gravity  tube  made  of 
rubber  with  small  stylet  to  fit  the  lumbar  puncture  nee- 
dle (Fig.  55).  The  stylet  of  the  gravity  tube  is  now  intro- 
duced into  the  lumbar  puncture  needle  and  the  vial  is  low- 
ered slightly  to  allow  the  air  bubbles  that  may  be  present 
in  the  gravity  tube  to  escape.  The  process  of  emptying  the 
vial  should  take  from  10  to  15  minutes.  If  more  than  15 
c.c.  of  serum  is  to  be  administered,  the  second  vial  is  at- 
tached to  the  gravity  tube  after  the  first  vial  has  been  emp- 
tied, and  the  fluid  allowed  to  run  in,  care  now  being  taken 
that  no  air  bubbles  are  allowed  to  enter  the  gravity  tube 
during  the  removal  of  the  vial. 

If  the  serum  does  not  flow  readily  into  the  spinal  canal 
the  vial  containing  the  serum  should  be  lowered  to  allow 
the  air  bubbles  to  rise  to  the  surface.  If  this  does  not  bring 
the  bubbles  to  the  surface,  squeezing  the  gravity  tube  may 
do  it.  This  should  be  done  very  cautiously,  however,  to 
prevent  the  pushing  of  air  bubbles  into  the  spinal  canal. 
If  the  serum  still  does  not  flow  into  the  canal,  it  is  advis- 
able to  use  a  small  stei-ile  bulb  on  the  vial  to  press  in  the 
fluid.     This  procedure  has  often  given  me  good  results. 


212  CEREBROSPIXAL    FLUID 

Some  authors  advise  the  washing  of  the  spinal  canal 
with  sterile  salt  solution  before  the  injection  of  the  serum. 
In  my  opinion  this  procedure  is  neither  necessary  nor  ad- 
visable. 


Fig.   55. — Instrument    for    the    introduction    of    antinieningococcus    serum    by    the    gravity 

method. 

As  for  the  dose  of  serum  to  be  administered  at  one  time, 
no  absolute  rule  can  be  given.  SoiDhiaii  advises  the  use  of 
blood  pressure  as  an  index,  a  marked  fall  in  blood  pressure 
being  an  indication  to  stop  the  injection  of  serum.  One 
may  always  guide  oneself  by  the  amount  of  fluid  removed 


INTRASPIiSrAL    TREATMENT  213 

inclining  toward  the  larger  rather  than  the  smaller  dose. 
For  example,  it  is  hest  to  adniinivster  30  c.e.  of  sernm 
the  first  time  if  it  is  possible  to  remove  30  e.c.  or  more 
of  cerebrospinal  fluid.  If  not  more  than  15  or  20  c.c.  of 
cerebrospinal  fluid  can  be  removed  at  one  sitting  an  at- 
tempt should  be  made  to  introduce  20  c.c.  of  serum.  If 
unsuccessful,  at  least  15  c.c.  of  the  serum  should  be  given. 
I  believe  that  the  principle  of  diphtheria  antitoxin,  that  as 
much  serum  as  possible  be  given  at  one  time,  can  be  ap- 
plied with  the  same  beneficial  effects,  to  the  administration 
of  antimeningococcus  serum. 

How  often  the  administration  of  serum  is  to  be  repeated 
is  also  a  question  that  has  not  yet  been  definitely  decided 
upon.  However,  much  can  be  learned  from  a  study  of  the 
cerebrospinal  fluid  and  the  clinical  findings  in  the  partic- 
ular case.  As  long  as  there  are  bacteria  present  and  as 
long  as  the  cells  are  numerous  and  the  patient's  temper- 
ature is  high,  it  is  advisable  to  administer  serum  twice  a 
day.  It  has  been  my  plan  to  administer  30  c.c.  of  serum 
the  first  time,  30  c.c.  the  second,  third  and  fourth  times, 
making  120  c.c.  in  all,  irrespective  of  the  cerebrospinal 
findings.  Then  if  the  temperature  continues  high  and  the 
cerebrospinal  fluid  shows  the  presence  of  many  cells  after 
waiting  one  day  I  administer  30  c.c.  additionally  even  if 
no  bacteria  are  present.  I  then  wait  two  days  longer 
and  if  the  case  shows  no  change  for  the  better  I  adminis- 
ter 30  c.c.  more.  The  following  case  illustrates  the  method 
I  usually  follow: 

March  24,  1917,  7  p.m.  F.  A.,  age  two  and  one-half  years  admitted  to 
hospital  with  symptoms  of  meningitis.  (Seo  Fig.  56.  Light  line,  pulse; 
black  line,  temperature.) 

March  24,  8  P.M.  Spinal  puncture  done,  45  c.c.  of  cloudy  fluid  removed 
under  increased  pressure  and  30  c.c.  of  antimeningococcus  semim  injected. 
Cerebrospinal  fluid  examination  showed  53,280  cells  per  cubic  millimeter,  98 
per  cent  of  which  were  polymorphonuclear.  Noguchi,  Ross-,Jones,  and  Nonne 
tests  were  all  positive.  Direct  smear  showed  pus  cells  and  gram-negative  in- 
tracellular diplocoeci   (meningococci). 

March  25,  8:30  a.m.  Spinal  puncture  done,  40  c.c.  of  yellowish,  cloudy- 
looking   fluid  removed  under   markedly   increased   pressure;   25   c.c.   of   serum 


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iNTRASPIlSrAL    TREATMENT  215 

injected.  Examination  showed  12,000  cells  per  cubic  millimeter,  principally 
l)olyniorplioniiclears.  Noguchi,  Ross-Jones  and  Nonne  were  all  positive. 
Meningococci  were  found  in  direct  smear. 

March  25,  11:30  P.M.  Thirty-five  c.c.  cloudy,  yellowish  fluid  removed 
under  slightly  increased  pressure  and  25  c.c.  of  senim  injected.  Bouillon 
cultures  made  March  24  showed  meningococci. 

March  26.  Twenty-five  c.c.  of  cloudy  fluid  withdrawn  and  25  c.c.  of  serum 
injected.  Few  meningococci  found  in  direct  smear,  no  growth  appeared  on 
cultures. 

March  27.  Thirty  c.c.  of  spinal  fluid  withdrawn  and  25  c.c.  of  serum  in- 
jected. Examination  showed  polymorphonuclears  85  per  cent,  lymphocytes  10 
per  cent,  large  mononuclears  5  per  cent.  Globulin  tests  positive.  No  gi-owth 
on  cultures. 

March  29.  Thirty  c.c.  serum  injected.  No  meningococci  found  in  direct 
smear  and  no  growth  on  cultures. 

April  2.  Cultures  made  on  March  30  and  31,  and  April  1  and  2  show  no 
growth. 

The  following  case  I  believe  illustrates  the  fallacy  of  ad- 
ministering antimeningococcus  serum  in  too  small  doses. 

D.  B.,  entered  the  hospital  with  a  history  of  restlessness,  fever,  and  con- 
vulsions. The  cerebrospinal  fluid  removed  on  entrance  to  the  hospital  showed 
352  cells  i)er  cubic  millimeter,  all  of  which  were  polymorphonuclears.  The 
direct  smear  showed  numerous  meningococci.  Fifteen  c.c.  of  antimeningo- 
coccus  serum  was  administered  intraspinally  and  repeated  in  12  hours.  A 
third  dose  of  15  c.c.  of  serum  was  given  the  next  day,  making  a  total  of  45 
c.c.  of  serum.  Since  no  organisms  could  be  found  in  the  cerel)rospinal  fluid 
withdrawn  by  the  third  lumbar  puncture,  the  physician  decided  not  to  ad- 
minister any  more  serum.  The  patient's  temperature  was  down  and  she  was 
discharged  from  the  hospital  as  cured.  Two  weeks  later  the  patient  was  re- 
admitted to  the  hospital  with  very  severe  meningeal  symptoms.  The  cerebro- 
spinal fluid  was  turbid  again  and  showed  meningococci.  Sufficient  serum  was 
administered  this  time.  Tlie  child,  however,  did  not  improve.  The  meningi- 
tis became  more  severe  and  the  patient  died  from  the  disease.  If  the  patient 
had  received  sufficient  serum,  she  would  most  likely  have  recovered  from  the 
disease  and  remained  well. 

If  no  serum  can  be  injected  into  the  spinal  canal  the 
serum  should  be  injected  intraventricularly,  especially  in 
the  case  of  infants.  The  procedure  consists  of  the  with- 
drawal of  a  certain  amount  of  cerebrospinal  fluid  from  the 
ventricles  of  the  brain  and  of  the  injection  into  the  ven- 
tricles of  the  brain  of  the  desired  amount  of  serum.  Tf  no 
cerebrospinal  fluid  can  be  obtained  from  either  the  spinal 
canal  or  ventricles,  no  attempt  should  be  made  to  inject 


216  CEREBROSPINAL    FLUID 

serum  into  tlie  spinal  canal,  but  should  be  injected  intra- 
venously. In  adults  the  brachial  vein  may  be  used.  In 
infants  tlie  scrum  may  be  injected  into  the  longitudinal 
sinus. 

Untoward  Effects  of  Serum 

There  are  very  few  complications  that  follow  the  injec- 
tion of  antimeningococcus  serum  and  those  that  do  occa- 
sionally present  themselves  are  not  severe  enough  to  coun- 
terindicate  the  use  of  the  serum  treatment.  Among  the 
untoward  effects  sometimes  following  the  injection  may  l)e 
mentioned : 

1.  Shock. 

2.  Aggravation  of  disease  symptoms — the  so-called 
serum  meningitis. 

3.  Serum  rash. 

Shock  occurs  in  a  small  percentage  of  cases.  The  symp- 
toms consist  of  respiratory  failure  and  contraction  of  the 
pupils.  The  skin  is  usually  pale  but  occasionally  there  is 
a  flush  of  the  skin  and  even  an  edema.  When  shock  does 
occur,  it  can  generally  be  attrilmted  to  the  too  rapid  intro- 
duction or  to  the  administration  of  too  large  an  amount  of 
serum.  As  a  matter  of  j)rophylaxis  it  is  therefore  important 
that  the  serum  be  introduced  very  slowl}^  and,  if  possil)le,  in 
amounts  not  larger  than  the  amount  of  cerebrospinal  fluid 
removed.  For  safetj^'s  sake  the  blood  pressure  should  l)e 
watched  and  the  serum  discontinued  if  the  pressure  fall  is 
extreme.  It  has  already  been  pointed  out  in  the  discussion 
of  lumbar  j)uncture  that  it  is  dangerous  to  remove  cere- 
brospinal fluid  from  a  patient  suspected  of  suffering  with 
meningitis  in  the  sitting  position,  because  of  the  risk  of  pro- 
ducing shock  and  even  death.  When  shock  does  occur,  the 
administration  of  serum  should  be  discontinued,  and  atro- 
pine in  fairly  large  doses  such  as  1/300  in  a  child,  and  1/100 
to  1/50  in  an  adult  should  l)e  administered  hypodermatically. 
This  method  of  treatment  has  given  me  very  good  results. 
If  the  atropine  does  not  relieve  the  symptoms,  one  c.c.  of 


INTRASPINAL   TREATMENT  217 

a  1:1000  solution  of  adrenalin  chloride  should  be  given 
hypodermatically.  The  occurrence  of  shock  should  not 
prevent  one  from  introducing  serum  intraspinally  into  the 
same  patient  several  hours  later.  In  such  cases,  I  would, 
however,  advise  the  administration  of  a  dose  of  atropine 
previous  to  the  giving  of  the  serum,  so  as  to  prevent  the 
repetition  of  the  occurrence. 

Aggravation  of  Symptoms 

Cases  have  been  described  in  which  the  patient  has  be- 
come more  ill  after  the  administration  of  serum  than  be- 
fore. The  exacerbation  of  symptoms,  however,  is  only  tem- 
porary and  should  not  arouse  any  anxiety. 

Serum  Rash 

Antimeningococcus  serum,  like  every  other  foreign  pro- 
tein introduced  into  the  body,  occasionally  gives  rise  to  a 
rash  that  makes  its  appearance  several  days  after  the  ad- 
ministration of  the  serum.  The  rash  may  be  macular  or 
papular,  but  it  usually  occurs  in  the  form  of  large  blotches 
similar  to  those  of  any  other  serum  rash.  The  eruption, 
as  a  rule,  occurs  on  the  fifth  or  sixth  day  after  the  adminis- 
tration of  the  first  dose  of  serum.  It  usually  starts  from 
the  point  of  injection  of  the  serum,  i.e.,  from  the  lumbar  re- 
gion. It  may  involve  only  a  portion  of  the  body  or  the 
entire  body.  Severe  symptoms,  such  as  nausea,  vomit- 
ing and  temperature  accompany  the  rash,  but  they  are 
generally  of  very  short  duration.  The  appearance  of  the 
rash  often  arouses  a  suspicion  of  the  coexistence  of  an  acute 
exanthematous  disease  such  as  scarlet  fever.  However,  the 
history  of  serum  injection  and  the  localization  of  the  rash 
can  generally  be  depended  upon  to  settle  the  diagnosis. 

Intraspinal  Treatment  of  Pneumococcus  Meningitis 

Of  late  the  use  of  antipneumococcus  serum  has  become  a 
matter  of  common  practice  in  the  treatment  of  pneumonia. 


218  CEREBROSPINAL    FLUID 

One  would,  therefore,  be  tempted  to  use  the  pneumoeoccus 
serum  intraspinally  in  the  treatment  of  pneumoeoccus  men- 
ingitis. Broadbent  reports  four  cases  of  pneumoeoccus 
meningitis  that  resulted  in  recovery  after  administration 
of  antipneumococcus  serum.  He,  however,  gave  the  serum 
to  his  patient  by  mouth.  Drought  and  Kennedy  consider 
intrathecal  injection  of  antipneumococcic  serum  mixed 
with  a  solution  of  sodium  oleate  as  the  most  promising 
method  of  treatment.  So  far  very  few  cases  have  been  re- 
ported in  A\'hieh  intraspinal  injection  of  antipneumococcus 
serum  has  been  used  and  of  those  that  have  been  reported, 
none  seem  to  have  been  followed  with  any  marked  degree 
of  success. 

Pneumoeoccus  A^accine  has  been  used  intraspinally  by  an 
English  physician  in  the  treatment  of  pneumoeoccus  men- 
ingitis. He,  however,  does  not  report  striking  results, 
either. 

Optochin  has  been  administered  by  some  intraspinally 
for  the  treatment  of  pneumoeoccus  meningitis.  I  saw  one 
case  of  pneumoeoccus  meningitis  in  Avhich  intraspinal  injec- 
tions in  one-half  grain  doses  of  optochin  (ethyl  cuprin  hy- 
drochloride) were  made  and  the  patient,  a  child  of  twelve, 
recovered.  The  case  in  question,  however,  had  also  had 
an  intraspinal  injection  of  antimeningococcus  serum 
previously  and  this  may  have  been  a  factor  in  the  recovery, 
for  another  case  in  which  optochin  was  used  did  not  re- 
spond favorably.  One  needs  to  see  more  than  one  case  of 
recovery  attributable  to  the  use  of  optochin  before  he  can 
endorse  its  use.  Those  who  have  used  horse  serum  in- 
traspinally do  not  report  any  apparent  results  from  its 
use.  In  general,  then,  one  can  not  make  any  positive 
statements  about  the  good  etfects  of  intraspinal  treat- 
ment in  pneumoeoccus  meningitis.  However,  until  some- 
thing better  can  be  found  1  would  advocate  repeated  lum- 
bar punctures  and  the  injection  of  polyvalent  antipneumo- 


INTRASPIKAL   TREATMENT  2l0 

COCCUS  serum,  or  even  ordinary  horse  serum  if  no  other  is 
obtainable,  into  the  spinal  canal. 

Intraspinal  Treatment  in  Tuberculous  Meningitis 

Of  the  numerous  remedies  advocated  and  tried  for  the 
treatment  of  tuberculous  meningitis,  none  have  been  at- 
tended with  success.  Weak  solutions  of  carbolic  acid,  cre- 
sol,  iodine  and  urotropine  have  been  ^iven  intraspinally. 
Tuberculin  in  various  dilutions  has  also  been  adminis- 
tered. Thus  far,  neither  intraspinal  treatment  nor 
any  other  form  of  treatment  has  been  of  any  value  in  tu- 
berculous meningitis.  A  few  cases  have  been  reported  in 
the  literature  here  and  there  of  tuberculous  meningitis  re- 
sulting in  recovery  with  healed  tubercles;  however,  from 
the  long  list  of  cases  that  culminated  in  death,  cases  re- 
ported both  in  the  literature  and  in  hospital  records,  one 
is  inclined  to  doul)t  the  diagnosis  of  "tuberculous  menin- 
gitis" in  those  cases  reported  as  having  recovered. 

Influenza  Meningitis 

Flexner  describes  a  serum  for  influenza  meningitis  that 
is  said  to  be  specific.  I  treated  several  cases  with  it  with- 
out any  favorable  results,  nor  did  I  find  any  cases  of  in- 
fluenza meningitis  reported  in  the  literature  as  having  re- 
covered. 

Poliomyelitis 

The  reports  of  Rosenow  and  Nuzum  speak  very  optimis- 
tically of  the  serum  treatment  of  epidemic  poliomyelitis. 
They  prepared  a  serum  which  they  claim  is  specific 
against  the  organism  found  by  them  in  the  brain  and  cord 
and  also  in  the  cerebrospinal  fluid  of  anterior  poliomyelitis. 
The  entire  question,  however,  of  the  serum  treatment  cf 
jjoliomyelitis  is  still  a  controversial  one,  so  that  it  is  im- 
])()ssible  at  present  to  say  just  what  valuation  can  be  placed 
on  tiie  intraspinal  treatment  of  poliomyelitis. 


220  CEREBROSPIXAL    FLUID 

The  Swift-Ellis  Treatment 

It  has  been  the  experience  of  many  workers  that  the  best 
results  in  the  treatment  of  syphilis  of  the  nervous  system 
are  obtained  by  introducing  salvarsan  (arsphenamine)  or 
neosalvarsan  (neoarsphenamine)  into  the  spinal  canal.  Sal- 
varsan or  neosalvarsan,  however,  has  too  irritating  an  ef- 
fect upon  the  meninges.  The  Swift-Ellis  treatment  is  there- 
fore more  efficient.  The  Swift-Ellis  treatment  is  based  on 
the  principle  that  the  blood  serum  of  syphilitics  who  have 
been  treated  with  neosalvarsan  has  a  curative  effect,  and 
that  the  best  results  are  obtained  when  salvarsanized  serum 
is  brought  into  direct  contact  with  the  central  nervous  sys- 
tem.   The  method  is  as  follows : 

Salvarsan  or  neosalvarsan  in  the  proper  dose  is  injected 
into  the  patient  intravenously,  usually  into  the  arm.  One 
hour  later  40  c.c.  of  blood  is  withdrawn  from  the  patient 
by  means  of  dry  syringe  and  needle  and  collected  into  a 
sterile  centrifuge  tube.  The  blood  is  allowed  to  coagulate. 
The  following  day  the  serum  is  centrifuged  for  one -half 
hour  till  all  the  cells  are  sedimented.  The  centrifuge  tube 
must  be  plugged  with  sterile  cotton  or  with  sterile  rubber 
caps  to  prevent  contamination  of  the  serum.  After  centri- 
fugation  12  c.c.  of  serum  is  carefully  pipetted  off  with  a 
graduated  pipette.  The  serum  is  diluted  with  18  c.c.  of 
normal  salt  solution,  making  a  total  of  40  per  cent  of 
serum.  This  mixture  is  heated  at  56°  C.  for  half  an 
hour.  Then  a  lumbar  puncture  is  performed,  15  to 
30  c.c.  of  cerebrospinal  fluid  is  removed  from  the  patient 
and  the  30  c.c.  of  the  serum-sodium  chloride  mix- 
ture is  warmed  to  body  temperature  and  injected  into 
the  spinal  canal.  Here  also,  as  in  any  other  intraspinal 
treatment  the  gravity  method  of  injection  should  be  used, 
to  obviate  the  danger  of  shock,  although  some  introduce 
the  serum  with  a  Luer  syringe  without  untoward  effects. 
Another  precaution  to  take  is  to  elevate  the  foot  of  the  bed 
<me  hour  after  the  injection.    The  patient  should  remain  in 


INTRASPINAL   TREATMENT  221 

bed  for  at  least  one  day  after  the  treatment.  The  treat- 
ment is  repeated  once  a  week,  till  the  Wassermann,  Lange 
and  globulin  tests  on  the  cerebrospinal  fluid  become  nega- 
tive, which  usually  takes  four  to  five  weeks. 

The  Swift-Ellis  treatment  has  many  critics.  Sachs,  for 
instance,  claims  that  marked  paresis  and  tabes  are  not 
influenced  favorably  by  this  form  of  treatment.  Halli- 
burton believes  that  ''the  intraspinal  injection  of  salvar- 
san  has  been  abandoned."  Yet  in  spite  of  the  various  ob- 
jections raised  the  Swift-Ellis  treatment  has  merit  and 
should  be  used  in  selected  cases  of  syphilis  of  the  nervous 
system.  I  would  only  emphasize  the  great  care  with  which 
it  has  to  be  carried  out  in  order  not  to  infect  the  patient 
and  thereby  set  up  a  suppurative  meningitis. 

Intraspinal  Treatment  of  Tetanus 

When  tetanus  antitoxin  is  used  as  a  prophylactic  meas- 
ure it  is  usually  injected  intramuscularly.  However,  when 
the  disease  is  fully  developed  intraspinal  injection  is  in- 
dicated. Tetanus  antitoxin  when  injected  into  the  blood 
has  been  found  to  appear  only  in  traces  in  the  cerebro- 
spinal fluid.  When  injected  directly  into  the  cerebrospinal 
fluid  by  the  intraspinous  method,  the  serum  comes  directly 
into  contact  with  the  tetanus  toxin  and  has  a  preventative 
if  not  a  curative  effect  on  the  tetanus.  Although  there  are 
other  ways  of  administering  tetanus  antitoxin,  the  intraspi- 
nal form  of  administration  is  one  of  the  most  efficient  in  the 
treatment  of  tetanus,  particularly  if  employed  in  sufficiently 
large  doses. 

The  method  used  in  administering  the  serum  is  the  same 
as  that  employed  for  the  administration  of  meningococcus 
serum,  namely,  the  withdrawal  of  cerebrospinal  fluid  and 
the  injection  of  the  serum  l)y  the  gravity  method,  in  a  some- 
Avhat  smaller  amount  than  that  of  the  fluid  withdrawn.  For 
instance,  if  20  c.c.  of  fluid  has  been  withdrawn,  about  15  c.c. 
of  serum  should  be  injected.     The  amount  injected  may 


222  CEREBROSPINAL   FLUID 

range  from  15  to  30  c.c.  depending  upon  the  quantity  of  fluid 
withdrawn.  The  intraspinal  administration  of  serum  by 
means  of  a  syringe  is  now  rarely  employed  in  the  treatment 
of  tetanus.  Intraspinal  injections  of  magnesium  sulphate  in 
the  treatment  of  tetanus  have  been  advocated  by  many 
authors,  notably  Meltzer. 

Intraspinal  Treatment  of  Chorea 

Chorea  has  been  treated  by  various  authors  by  injecting 
some  substance  into  the  spinal  canal  of  the  patient.  Lacuna 
used  intraspinal  injections  of  magnesium  sulphate. 
Goodman  used  autoserum  treatment  and  Porter  used  horse 
serum.  The  intraspinal  magnesium  sulphate  injection 
produced  no  beneficial  results  in  the  cases  reported  by 
Heiman,  Goodman  reported  a  series  of  cases  which  he 
claimed  Avere  benefited  by  his  autoserum  treatment,  which 
is  administered  in  the  following  manner: 

The  child  is  put  to  bed  for  four  days  or  longer  without 
medication.  At  the  end  of  this  period  45  or  50  c.c.  of  blood 
is  withdrawn  from  a  vein  and  rapidly  centrifuged.  The 
supernatant  l)lood  serum  is  tlien  pipetted  and  kept  on  ice. 
A  lumbar  puncture  is  made  and  about  20  c.c.  of  cere- 
brospinal fluid  is  withdrawn.  The  blood  serum  is  now 
heated  to  body  temperature  and  15  to  18  c.c.  of  serum  is  in- 
jected very  slowly  into  the  spinal  canal.  The  patient 
should  be  made  to  retain  the  recumbent  position  for  at 
least  one  hour  after  injection.  One  injection  is  usually 
sufficient.  Occasionally,  however,  it  is  necessary  to  give 
two,  three,  or  even  four  injections. 

Bibliogfraphy 

Amoss:     Notes  on  Tlie  Stan-dardization  and  Adiniuistiation  of  Autinieningo- 

coccic  Serum,  Jour.  Am.  Med.  Assn.,  1917,  Ixix,  1137. 
Amoss  and  Chcsney:     Serum  Treatment  of  Poliomyelitis,  Jour.  Exper.  Med., 

1917,  XXV,  581. 
Broadhent:      Ti^eatment  of  Pneumococcic  Meningitis,  Brit.  Med.  Jour.,  1916, 

586. 
Flexner:      Experimental  Cerebrospinal   Meningitis   and   its   Serum   Treatment, 

Jour.  Am.  Med.  Assn.,  1906,  xlvii,  560. 


INTRASPINAL   TREATMENT  223 

Flexner  and  Jobling:      Serum   Treatment  of   Epidemic  Cerebrospinal  Menin- 

});itis,  Jour.  Exper.  Med.,  lOOS,  x,  141. 
Goodman:     The  Auto-Seruin  Treatment  of  Chorea,  Arch.  Pediat.,  1916,  xxxiii, 

649. 
Groppert:     Ueber  Genickstarre,  Ergel).  der  Inneron  Med.,  1909,  iv,  165. 
Jochmann :     Versuche  zur  Bcrodiafinostik  und  Herotherapie  der  epidemischen 

Geniekstarre,  Deutsch.  mod.  Wchnschr.,  1906,  xxxii,  788. 
Levinson:     Pneumoc-occus  Meningitis,  Illinois  Med.  Jour.,  1917,  xxxii,  270. 
McCoy,   Wavson   and   Corbitt :      Potency   of   ATitimeningococcic   Serum,   Jour. 

Am.  Med.  Assn.,  1918,  Ixxi,  246. 
Neal  and  Abramson :     A  Comparison  of  Tricresol  and  Chloioform  as  a  Pre- 
servative in  Antimeningitic   Serum,   Jour.   Am.   Med.   Assn.,   1917,  Ixviii, 

1035. 
Nuzum :      The    Production    of   an    Antipoliomyelitic  Serum,    Jour.    Am.    Med. 

Assn.,  1917,  Ixviii,  24. 
Nuzum  and  Willy:     Specific  Serum  Therapy  of  Epidemic  Poliomyelitis,  Jour. 

Am.   Med.   Assn.,   1917,  Ixix,  1247. 
Porter:     Intrathecal  Injection  of  Horse  Serum  in  the  Treatment  of  Chorea, 

Am.  Jour.  Dis.  Child.,  1918,  xvi,  109. 
Rosenow:      The   Production   of   an   Antijioliomyelitis    Serum   in    Horses,   Jour. 

Am.  Med.  Assn.,  1917,  Ixiv,  261. 
Sachs:      Truth    About    Intraspinal    Injections    in    Treatment    of    Syphilis    of 

Nervous  System,  Jour.  Am.  Med.  Assn.,  1917,  681. 
Swift:      Intraspinal   Treatment   of   Syphilis   of   the  Central   Nervous   System, 

Jour.  Am.  Med.  Assn.,  1917,  Ixix,  2092. 
Swift  and   Ellis:      The   Direct   Treatment  of  Syphilitic  Diseases  of  the   Cen- 
tral Nervous  System,  New  York  Med.  Jour.,  1912,  xcvi,  53. 
The   Treatment   of    Syphilitic   Affections   of   the    Central   Nervous    System, 

with  Especial  Reference  to  the  Use  of  Intraspinous  Injection,  Arch.  Int. 

Med.,  1913,  xii,  331. 


CHAPTER  IX 
SUMMARY 

I  have  endeavored  to  show  the  varied  character  of  the 
cerebrospinal  fluid  in  health  and  in  disease.  In  the  con- 
sideration of  normal  fluid  the  following  facts  were  empha- 
sized: (1)  that  the  fluid  is  colorless;  (2)  that  it  circulates 
in  the  cerebrospinal  canal;  (3)  that  most  of  it  is  absorbed 
along  the  spinal  cord  and  some  of  it  in  the  cavity  of  the 
brain;  (4)  that  it  is  impermeable  to  most  chemicals;  (5) 
that  it  exerts  a  protective  function.  Even  under  normal 
conditions  cerebrospinal  fluid  is  a  most  complex  fluid  con- 
sisting of  from  98.602  to  99.124  parts  of  water  and  0.876  to 
1.398  of  solids.  The  protein  content  of  the  fluid  which  is 
very  small  ranges  from  0.013  to  0,07  per  cent;  the  mineral 
content,  consisting  principally  of  chlorides  and  carbonates, 
ranges  from  0.850  to  0.950  gm.  per  100  c.c.  The  other  ele- 
ments contained  in  the  fluid,  are  in  the  main,  the  same  as 
those  found  in  other  body  fluids,  although  the  proportions 
are  different. 

I  have  also  pointed  out  the  fact  that  the  H-ion  concentra- 
tion of  normal  cerebrospinal  fluid  is  practically  the  same  as 
that  of  the  blood  (7.4-7.6)  and  that  CO2  plays  an  important 
role  in  governing  the  reaction  of  the  fluid,  running  parallel 
with  the  H-ion  concentration. 

In  the  discussion  of  pathologic  fluid,  I  pointed  out  the 
fact  that  there  are  two  types  of  changes :  systemic  and  men- 
ingitic,  and  that  the  meningitic  changes  are  qualitative  as 
well  as  quantitative  and  that  the  former  are  of  as  great  if 
not  greater  significance  than  the  latter.  This  was  demon- 
strated by  means  of  the  cataphoresis  tube,  of  specific  pre- 
cipitation and  various  other  tests. 

224 


SUMMARY  225 

As  to  the  factors  responsible  for  tlie  qualitative  changes 
in  various  diseases  no  satisfactory  explanation  has  yet  been 
offered,  but  numerous  investigations  have  convinced  me 
that  the  changes  are  intimately  associated  with  the  hydro- 
gen-ion concentration.  The  marked  differences  noted  in 
the  H-ion  concentration  of  different  forms  of  meningitis 
bear  out  this  contention. 

In  the  discussion  of  teclmic  I  described  both  the  manner 
of  withdrawing  cerebrospinal  fluid  from  the  body  and  the 
method  of  examining  it  after  withdrawal.  Particular  at- 
tention was  given  to  those  methods  that  are  simple  and 
practical  enough  to  be  employed  by  the  physician  who  has 
no  extensive  laboratory  facilities. 

Under  changes  in  the  cerebrospinal  fluid  in  different  con- 
ditions, I  pointed  out  the  various  changes,  their  diagnostic 
significance  and  their  relation  to  the  clinical  manifestations 
of  the  disease. 

In  the  chapter  on  intraspinal  treatment  I  described 
both  the  methods  of  treatment  definitely  established  and 
those  still  in  the  experimental  stage. 

In  conclusion,  I  should  like  to  call  attention  to  the  fol- 
lowing lines  of  research  which  I  believe  are  of  fundamental 
value  in  clearing  up  some  of  the  contested  problems  in 
medicine. 

1.  The  origin  and  function  of  the  cerebrospinal  fluid. 

2.  The  chemical  and  physicochemical  changes  taking 
place  in  the  fluid  in  various  diseases  and  the  principles 
underlying  these  changes.  The  study  of  this  subject  will 
also  shed  light  on  the  origin  of  the  cerebrospinal  fluid. 

3.  The  chemical  and  physicochemical  relation  between 
the  cerebrospinal  fluid  and  other  body  fluids,  especially 
blood. 

4.  The  crystallization  of  the  cerebrospinal  fluid. 

The  solution  of  these  problems  will  open  limitless  oppor- 
tunities for  research  not  only  in  the  field  of  cerebrospinal 
fluid,  but  in  that  of  every  other  body  fluid. 


226  CEREBROSPIIS^AL    FLUID 


APPENDIX 
Monographs  on  Cerebrospinal  Fluid 

Anglada:  Le  liquide  ceplialo-rachidien  et  le  diagnostic  par.  la  poiiction  lom- 
baire,  Baillieie  et  fils,  Paris,  1909. 

Blumenthal :     Uber  Cerebrospinalfliissigkeit,  Ergebnisse  d.  Physiol.,  1902,  i,  1. 

Dircksen :  Liquide  Cephalo-Reeidien  y  Composition  chimique  et  Concentra- 
tion Moleculaire  These  de  Paris,  1901. 

Mestrezat:  Le  liquide  cephalo-rachidien  normal  et  pathologique.  Valeur 
clinique  et  I'examen  eliimique.  Syndromes  humoraux  dan  diverges  affec- 
tions, A.  Malloine,  Paris,  1912. 

Magendie:  Recherches  Physiologiques  et  Clinques  sur  le  Liquide  Cephalo- 
Rachidien  on  Cerebrospinal,  Paris,  1842. 

Milian:      Le  liquide   cephalo-rachidien,   Steinheil,   Paris,   1901. 

Nonne:      Sj^hilis  und   Nervensystem,  Achtzehnte  Vorlesung. 

Plaut:  Die  Wassermannsche  Serodiagnostik  der  Syphilis  in  ihrer  Anwend- 
ung  auf  die  Psycliiatrie,  Fischer,  Jena,  1909. 

Plaut,  Rehm  and  Schottmiiller :  Leitfaden  zur  Untersuchung  der  Zerebro- 
spinalfliissigkeit,  Fischer,  Jena,  1913. 

Quincke:      uber  Lumbalpunktion,  Die  deutsche  Klinik  am   Eingange   des  20. 
Jahrhunderts,  1906,  vi,  1,  351. 
English  translation:     Diseases  of  the  Nervous  System,  1910,  223. 

Rehm:  Die  Cerelirospinalfliissigkeit,  physikaJische,  ehemische  und  cyto- 
logische  Eigenschaften  und  ihre  klinische  Verwertung.  Ilistologische 
und  histopathologische  Arbeiten  iiber  die  Grosshirnrindc  (Nissl  und 
Alzheimer),  1909,  iii,  1,  p.  201. 

Sicard:      Le   liquide   cephalo-rachidien,   Masson   et   Cie.,   Paris,   1902. 

Sorrentino:     Semeilogia  del  liquido  cefalo-rachidiano,  Napoli,  1915. 

Thomson:     The  Cerebrospinal  Fluid,  William  Wood  &  Co.,  1901. 


INDEX 


A 

Absorption    of    cerebrospinnal    fluid, 

34,  36 
Acidity    of    cerebrospinal    fluid    (see 
Eeactiou    of    cerebrospinal 
fluid) 
AgjJ-lutination,  147 

of  meningococci,   172,   198 
of  pneumococci,  176,  202 
Alkaline      reserve      of      cerebrospinal 
fluid : 
in  meningococcus  meningitis, 

196 
in      tuberculous      meningitis, 

192 
normal,  lOo 
pathologic,  132 
Alkalinity  of  cerebrospinal  fluid,  44 
Amount  of  cerebrospinal  fluid: 
increase  in,  116 
ill     meningococcus     meningitis, 

194 
in  tuberculous   meningitis,  190 
normal,  76 
Amylolytic  power  of  normal  cerebro- 
spinal fluid,  107 
Anatomy  of  cerebrospinal   fluid,  30 
of  chorioid  plexus,  31 
of  subarachnoid  space,  30 
Antimeningococcus  serum : 

amount  administered,  212,  213 
cerebrospinal    fluid    after    treat- 
ment with,  199 
in  agglutination  of  meningococci, 

172,  173,  175 
indications  for,  210 
intraspinal  treatment  with,  209 
methods  of  preservation,   210 
methods  of  production,  210 
methods  of  testing  potency  of,  210 
precipitation      of      cerebrospinal 

fluid  with,  176 
technic  of  introduction,  211 
untoward  effects  of,  216 
Antipneuniococcus    serum    in    aggluti- 
)iation  of  piunimococci,  176 
in    treatment     of     pneumococcus 
meningitis,  217,  218 


B 

Bacteriology    of    cerebrospinal    fluid, 

general    consideration    of, 

146 
in  colon  meningitis,  203 
in   influenza   meningitis,   203 
in  meningococcus  meningitis, 

196,   197,   198 
in   pneumococcus   meningitis. 

200,  201,  202 
in  poliomyelitis,   207 
in    streptococcus    meningitis, 

202 
in     tuberculous     meningitis, 

193 
methods  employed,  171 
Biometer,    144 

C 

Carbonates  in  nonmeningitic  cerebro- 
spinal fluid,  88 
Carbon    dioxide,    amount    in    normal 
fluid,  87,  91 
effect    on   the   hydrogen-ion    con- 
centration   of    fluid,    102, 
103,  142,  144 
Cataphorcsis,  134 

in   meningococcus    meningitis,    136, 

196 
in  tuberculous  meningitis,  135,  193 
Cells  in   cerebrospinal   fluid    (see  Cy- 
tology) 
Cerebrospinal  fluid: 
anatomy  of,  30 

location   of,  30 
history  of,  17 
physiology  of,  30 
absorption  of,  36 
circulation   of,  33,  35 
formation   of,   34 

rate  of,  34 
function  of,  40 
origin  of,  41 
in  various  diseases,  183 
methods  of  examination,  150 
nietliods   of    obtaining,   49 
cranial  puncture,  71 
lunil)ar  puncture,  49 


227 


228 


INDEX 


Cerebrospinal  fluid — Cont  'd 
properties  of, 

normal,   75,    {see  Normal  cere- 
brospinal  fluid) 
pathologic,    113 
Chemistry  of  cerebrospinal   fluid: 
normal,  79 
pathologic,   123 
Chlorides  in  cerebrospinal  fluid : 
meningitic,  131,  191 
method  of  determination,  161 
nonmeningitic,  87,  91 
Cholesterol  in  cerebrospinal  fluid,  130 
Cholin,  130 

Chorea,  cerebrospinal  fluid  in,   183 
Chorioid  plexus: 

blood  supply  cf,  31 
structure  of,  31 
Circulation  of  cerebrospinal  fluid,  33, 

35 
Collection      of      cerebrospinal      fluid, 
method   of,   69    {see  Lum- 
bar puncture) 
Colloidal     gold     reaction,     137     {see 
Lange  gold  chloride  test) 
Colon  meningitis,  203 
Color  of  cerebrospinal  fluid: 

in  compression  of  cord,  189 
in  hemorrhage  of  brain,  188 
in  meningococcus  meningitis, 

194 
in  pneumococcus  meningitis, 

200 
normal,  76 
pathologic,  150 
Composition    of    cerebrospinal     fluid, 

{see  Chemistry) 
Compression     of    the    cord,    cerebro- 
spinal fluid  in,  189 
Conductivity  of  cerebrospinal  fluid: 
normal,  95 
pathologic,  132 
Cranial  puncture,  indications  for,  71 

technic  of,  71 
Crystallization  of  cerebrospinal  fluid: 
normal,  88 
pathologic,  120 
Cytology  of  cerebrospinal  fluid: 
normal,  108 

number  of  cells,  108 
type  of  cells,  110 
pathologic,  117 
chorea,  183 

compression   of  cord,  189 
encephalitis,   189 
epilepsy,  184 
influenza   meningitis,   203 
lues.  186 


Cytology      of     cerebrospinal     fluid — 

Cont  'd 
meningism,   190 
meningococcus        meningitis, 

196 
p  n  e  u  m  o  coccus   meningitis, 

200 
poliomyelitis,  207 
psychoses,  185 

streptococcus  meningitis,  202 
syphilitic  meningitis,  203 
tuberculous  meningitis,  190 
tumor  of  brain,  189 
technic  employed,  167 

D 
Diabetes  mcllitus,  cerebrospinal  fluid 

in,  130,  183 
Dry  puncture,  63 

E 
Elimination  of  phenolphthalein  from 

subarachnoid  space,  36 
Encephalitis,    cerebrospinal    fluid    in, 

189 
Ejulepsy,  cerebrospinal  fluid  in,    184 
Examination    of    cerebrospinal    fluid, 
methods  of,  150 
bacteriologic,  171 
culture  media,  171 
direct  smear,  172 
chemical,  152 
chlorides,  161 
globulin,  153 
permanganate,  157 
protein,    152 
sugar,   158 
cytologic,   167 

Chamber  method,   168 
French   method,   167 
guinea  pig  inoculation,  177 
immunologic,  172 
agglutination,  172 
neutralization  test,  177 
precipitin  test,  176 
Wasscrmann,   177 
neutralization  test,  177 
physical,  color,  150 
foam,   151 
pellicle,  151 
physicochemical,   162 
Lange,  164 
Mastic,  166 
F 
Fibrin  ferment  in  cerebrospinal  fluid: 
normal,  107 
pathologic,   119 
Foam     in     pathologic     cerebrospinal 
fluid,  117 


INDEX 


229 


Formation  of  cerebrospinal  fluid,  34 
Freezing  point  of  cerebrospinal  fluid: 

normal,  95 

pathologic,  132 
Function  of  cerebrospinal  fluid,  40 

G 

Globulin  in  cerebrospinal  fluid : 

in     meningococcus     meningitis, 
125,  195 

in     pneumococcus     meningitis, 
200 

in  poliomyelitis,  205 

in      streptococcus      meningitis, 
202 

in  tuberculous  meningitis,  125, 
191 

relative  value  of  various  tests, 
156 

tests  for,  153 
Glycolytic  ferment  in  normal  cerebro- 
spinal fluid,  107 
Guinea  pig  inoculation,  177,  193 


Hemolysin  in  cerebrospinal  fluid : 
lack  of,  in  normal,  108 
presence  of  in  pathologic,   147 
Hemorrhage    of    brain,    cerebrospinal 

fluid  in,  188 
History  of  cerebrospinal  fluid,  17 
Hydrocephalus,  cerebrospinal  fluid  in, 

188 
Hydrogen-ion    concentration    of    cere- 
brospinal  fluid: 
general  consideration  of,  96 
methods   of  determination,  163 
normal  fluid,  corked,  102 
fresh,  97 
old,   97 
pathologic,     in     meningococcus 
meningitis,  141,  196 
in     tuberculous      meningitis, 
141.   192 


Immunology,  147 
agglutination,  147 
methods  of,  172 
•hemolysin,  147 

Wassermann,  148 
Influenza     meningitis,     cerebrospinal 

fluid   in,   203 
Inoculation    with    cerebrospinal    fluid, 

177,  193 
liitraspinal  treatment: 
of  chorea,  222 
of  influenza  meningitis,  219 


Intraspinal  treatment — Cont  'd 

of  meningococcus  meningitis,  209 
of  pneumococcus  meningitis,  217 
of  poliomyelitis,  219 
of   syphilis    of   the    nervous    sys- 
tem, 220 
of  tetanus,  221  • 


Langp  gold  chloride  test,  137 

in  cerebrospinal  lues,  186 

in  general  paresis,  186 

in  meningococcus  meningitis, 

196 
in  poliomyelitis,   205 
in  tabes,  186 
in      tuberculous      meningitis, 

192 
technic,    164 
Location  of  cerebrospinal  fluid,  30 
lilies,  cerebrospinal  fluid  in,  185 
Lumbar  puncture,  49 

history  of,  24,  25,  49 
indications  for,  49 
reasons  for  failure,  63 
structures  encountered  in,  56 
technic  of,  54 

measurement  of  pressure,  64 
needle  used,  57 
untoward  effects  of,  53 

M 

Mastic  reaction,  137 

technic  of,  166 
Meninges,  permeability  of,  38 
Meningism,     cerebrospinal     fluid     in, 

190 
Meningitis,  cerebrospinal  fluid  in: 
colon,  203 
influenza,  203 

meningococcus,    194    (see    Me- 
ningococcus meningitis) 
pneumococcus,   200    (see  Pneu- 
mococcus meningitis) 
streptococcus,  202 
syphilitic,  203 

tuberculous,  190   (see  Tubercu- 
lous meningitis) 
Meningococcus     meningitis,     cerebro- 
spinal fluid  in : 
amount,  194 
alkali  reserve,  196 
bacteriology,  196,  198 
chemistry,  196 
color,  194 
cytology,  196 
Lange  gold  chloride,  196 
pellicle,  194 


230 


INDEX 


Meningococcus     meningitis,     cerebro- 
spinal fluid  in — Cont'd 
physicochemical    changes,    196 
pressure,  194 
sediment,   195 
intraspinal  treatment,   209 
0  Mongolian  idiocy,  cerebrospinal   fluid 
in,  184 

N 

Neutralization    test    in    poliomyelitis, 

177 
Ninhydrin  reaction,  137 
Normal   cerebrospinal   fluid,    75 
amount,  76 

biochemical  properties,   107 
chemistry  of,  79 

table  of  composition,  91,  92 
color,  76 
cytology  of,  108 
physical    properties,    76 
physicochemical  properties  of: 
alkaline  reserve,  105 
conductivity,   95 
freezing  point,  95 
hydrogen-ion     concentration, 

of,  96 
reaction  of,  96 
refractometric  index  of,  96 
specific  gravity  of,  79,  94 
surface  tension  of,  95 
viscosity  of,  95 

O 

Organic  index  {see  Permanganate 
index  of  cerebrospinal 
fluid) 

Origin  of  cerebrospinal  fluid,  41 


Pellicle  in  cerebrospinal   fluid,   118 

in     meningococcus     meningitis, 

194 
in     pneumococcus     meningitis, 

201 
in  tuberculous  meningitis,   191 
Permanganate  index  of  cerebrospinal 
fluid,  85 
normal,  86 
pathologic,   123 
technic,   157 
Permeability  of  meninges,  38 
Phonolphthalcin,  elimination  of,  from 

subarachnoid    space,    36 
Physical    chemistry    of    cerebrospinal 
fluid : 
normal,  94 
pathologic,  132 


Physiology  of   cerebrospinal   fluid,  30 
Pneumococcus      meningitis,      cerebro- 
spinal fluid  in: 
agglutination,  202 
amount,  200 
bacteriology,  200 
chemical  analysis,  200 
color,  200 
pellicle,  201 

physicochemical  changes,  200 
protein,  200 
sediment,   200 
intraspinal  treatment,  217 
Poliomyelitis,  cerebrospinal  fluid  in: 
amount,    205 
bacteriology,  207 
cytology,  207 

Lange  gold  chloride  test,  205 
permanganate  index,   205 
pressure,  205 
protein,    205 
intraspinal  treatment   in,   219 
Precipitation    of    cerebrospinal    fluid, 
125 
metallic   and  alkaloidal,   126 
methods,  153 

Avith  antimeningococeus  serum, 
176 
Pressure  of  cerebrospinal  fluid: 
method  of  measuring,  64 
normal,  77 
pathologic,    116 
Protein  of  cerebrospinal  fluid: 

in     meningococcus     meningitis, 

195 
in  tuberculous  meningitis,  191 
method  of  determination,  152 
normal,  81,  82,  83,  84,  91 
pathologic,  125 
protein  charges,  133 
Proteolytic  power  of  normal  cerebro- 
spinal fluid,  107 
Psychoses,  cerebrospinal  fluid  in,  185 

E 

Rate    of    formation    of    cerebrospinal 

fluid,  34 
Reaction  of  cerebrospinal  fluid : 
normal,  96 
pathologic,  138 
Refractometric  index  of  normal  cere- 
brospinal fluid,  96 

S 
Sediment   in   cerebrospinal   fluid,  lack 
of,  in  normal,  76 
meningococcus    meningitis,    195 

(see  Pellicle) 
tuberculous  meningitis,   191 


INDEX 


231 


Serum  rash,  217 

Specific      gravity      of      cerebrospinal 
fluid: 
normal,  79,  94 
pathologic,  132 
Spina    bifida,    cerebrospinal    fluid    in, 

188 
Streptococcus      meningitis,      cerebro- 
spinal fluid  in,  202 
Sugar  in  cerebrospinal  fluid : 

methods  of  determination,  1.38 
normal,  83,  84,  86,  91 
pathologic,  129,  130,  183,  191, 
196 
Surface    tension    of    normal    cerebro- 
spinal fluid,  95 
Swift-Ellis  treatment,  220 
Syphilitic   meningitis,   203 

T 

Tuberculous  meningitis,  cerebrospinal 

fluid  in,  190 
amount,   190 
cataphoresis,  193 
chemical  changes,  191 
h  y  d  r  ogen-ion      concentration, 

192 
inoculation  with,  193 
Lange  gold  chloride,  192 
pellicle,   191 

permanganate  index,  191 
physicochemical  changes,  191 
pressure,  190 
transparency  of,  191 
tubercle  bacilli  in,  193 
viscosity,  191 


Tumors   of   brain,   cerebrospinal   fluid 

in,  189 
Turbidity  of  cerebrospinal  fluid,  131 

U 

Urea  in  cerebrospinal  fluid,  89 

nonmeningitic,  89 

normal,  94 

pathologic,  130 
Uremia,  cerebrospinal  fluid  in,  183 


Viscosity  of  cerebrospinal  fluid : 

in  meningococcus  meningitis, 

196 
in     tuberculous      meningitis, 

191 
normal,  95 
pathologic,  132 

W 

Wassermann  reaction,  148 
in  cerebrospinal  lues,  186 
in  chorea,  184 
in  general  paresis,  186 
in  mongolian   idiocy,  184 
in  psychoses,  185 
in  syphilitic  meningitis,   203 
in  tabes,  186 
principle,  178 
technic,  179 

X 

Xanthocromia,  151,  189 


Date  Due 

1 

PRINTED  IN  U.S.A.                 CAT.     NO      24     161                     Bw 

WL203 
l65Tc 
1919 


Levinson,  Abraham 
Cerebrospinal  fluid 


Levinson,  Abraham 
Cerebrospinal  fluid 


WL203 
l657c 
1919 


MEDICAL  SCIENCES  LIBRARY 

UNIVERSITY  OF  CALIFORNIA,  IRVINE 

IRVINE,  CALIFORNIA  92664 


